{"entity": "journal", "iuid": "b3a57cbfb0f742c0bf54fb5e8e7a8194", "timestamp": "2026-07-15T07:03:03.231Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Cancer%20Res..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Cancer%20Res."}}, "title": "Cancer Res.", "issn": "1538-7445", "issn-l": "0008-5472", "publications_count": 25, "publications": [{"entity": "publication", "iuid": "36236e6be0ce4b17b39f3a3841e121fb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/36236e6be0ce4b17b39f3a3841e121fb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/36236e6be0ce4b17b39f3a3841e121fb"}}, "title": "Dissecting FAP+ Cell Diversity in Pancreatic Cancer Uncovers an Interferon-Response Subtype of Cancer-Associated Fibroblasts with Tumor-Restraining Properties.", "authors": [{"family": "Cumming", "given": "Joshua", "initials": "J", "orcid": "0000-0003-3661-7443", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd0f3e688ff047ef8e814134c0446774.json"}}, {"family": "Maneshi", "given": "Parniyan", "initials": "P", "orcid": "0000-0002-2180-4097", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c23ae21a4df4f319d2395580aa4fb2e.json"}}, {"family": "Dongre", "given": "Mitesh", "initials": "M", "orcid": "0000-0002-7151-1137", "researcher": {"href": "https://publications.scilifelab.se/researcher/6acd00be909d41399277be66d9600d41.json"}}, {"family": "Alsaed", "given": "Tala", "initials": "T", "orcid": "0009-0009-5690-5929", "researcher": {"href": "https://publications.scilifelab.se/researcher/58e2e9329f714da7ad4892b11a3c726d.json"}}, {"family": "Dehghan-Nayeri", "given": "Mohammad Javad", "initials": "MJ", "orcid": "0009-0002-1538-4871", "researcher": {"href": "https://publications.scilifelab.se/researcher/8399aab605474070a84399a52d4befe2.json"}}, {"family": "Ling", "given": "Agnes", "initials": "A", "orcid": "0000-0002-9503-0784", "researcher": {"href": "https://publications.scilifelab.se/researcher/acb1fab24b604772bf2bb07fc10c056d.json"}}, {"family": "Pietras", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6738-4705", "researcher": {"href": "https://publications.scilifelab.se/researcher/5be0a3ec07654822a91df964eab1d6e4.json"}}, {"family": "Patthey", "given": "Cedric", "initials": "C", "orcid": "0000-0002-2627-9578", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b7707e8bd3d4e029fb1e1f43df86ad4.json"}}, {"family": "\u00d6hlund", "given": "Daniel", "initials": "D", "orcid": "0000-0002-5847-2778", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e9e473f68c460098a37e22d0a41369.json"}}], "type": "journal article", "published": "2025-07-02", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "85", "issue": "13", "pages": "2388-2411", "issn-l": "0008-5472"}, "abstract": "Within the stroma of pancreatic ductal adenocarcinoma (PDAC), mesenchymal cells differentiate into cancer-associated fibroblast (CAF) subtypes that differentially mediate disease progression. Defining the regulatory mechanism and diversity of CAF subtypes could identify potential therapeutic strategies to harness the tumor-suppressive activities of CAFs. To address this, we utilized single-cell RNA sequencing to profile fibroblast activation protein-\u03b1 (FAP)-expressing mesenchymal cells in human PDAC. The mesenchymal subpopulations in PDAC reflected mesenchymal cell heterogeneity found in the normal developing pancreas. In addition to characterizing inflammatory CAF and myofibroblastic CAF subpopulations in detail, the analysis uncovered a previously undescribed interferon-response CAF (ifCAF) subtype. Tumor-derived signals induced specific CAF subtypes from pancreatic stellate cells in an organoid-based coculture model, and time-course experiments revealed regulatory mechanisms that govern subtype formation. STING agonists promoted an ifCAF phenotype in vivo and in vitro. Importantly, induction of an ifCAF phenotype suppressed tumor cell invasiveness and induced an antitumor phenotype in tumor-associated neutrophils. Together, this study resolves FAP+ stromal cell heterogeneity in PDAC and identifies an ifCAF subtype that can be induced to suppress protumorigenic features of PDAC.\n\nCharacterization of FAP+ mesenchymal cell heterogeneity in pancreatic cancer identifies a tumor-suppressive interferon-response cancer-associated fibroblast subtype that can be induced by stimulating type I interferon signaling using STING agonists.", "doi": "10.1158/0008-5472.CAN-23-3252", "pmid": "40215177", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service", "Clinical Genomics": "Service", "Clinical Genomics Ume\u00e5": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12214878"}, {"db": "pii", "key": "757349"}], "notes": [], "created": "2025-11-21T18:45:35.492Z", "modified": "2025-11-28T10:52:09.338Z"}, {"entity": "publication", "iuid": "29e8b95c6ed0495fa4bd99c2842477e1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/29e8b95c6ed0495fa4bd99c2842477e1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/29e8b95c6ed0495fa4bd99c2842477e1"}}, "title": "Abstract 2025: Zeb1 downregulation sensitizes pancreatic cancer-associated fibroblasts to killing by oncolytic reovirus through upregulation of the reovirus receptor junction adhesion molecule A", "authors": [{"family": "Dam", "given": "Nicole", "initials": "N"}, {"family": "Harryvan", "given": "Tom J", "initials": "TJ"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Hawinkels", "given": "Lukas J A C", "initials": "LJAC"}, {"family": "Kemp", "given": "Vera", "initials": "V"}], "type": "journal-article", "published": "2024-03-22", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "issn-l": "0008-5472", "volume": "84", "issue": "6_Supplement", "pages": "2025-2025"}, "abstract": null, "doi": "10.1158/1538-7445.am2024-2025", "pmid": null, "labels": {"CRISPR Functional Genomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2024-10-02T06:45:12.313Z", "modified": "2026-03-18T09:42:23.232Z"}, {"entity": "publication", "iuid": "b4ff3ca17be540cbb545c1a64ee4e126", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4ff3ca17be540cbb545c1a64ee4e126.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4ff3ca17be540cbb545c1a64ee4e126"}}, "title": "Erythroid Differentiation Enhances RNA Mis-Splicing in SF3B1-Mutant Myelodysplastic Syndromes with Ring Sideroblasts.", "authors": [{"family": "Moura", "given": "Pedro L", "initials": "PL", "orcid": "0000-0002-0493-5394", "researcher": {"href": "https://publications.scilifelab.se/researcher/12216bfd20fa4056b844842908efc829.json"}}, {"family": "Mortera-Blanco", "given": "Teresa", "initials": "T", "orcid": "0000-0002-8399-1430", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a4cccc1f92842b78d19b5c232a655fe.json"}}, {"family": "Hofman", "given": "Isabel J", "initials": "IJ", "orcid": "0000-0001-7825-843X", "researcher": {"href": "https://publications.scilifelab.se/researcher/28b2678b6e1d45299c3a446b4f305762.json"}}, {"family": "Todisco", "given": "Gabriele", "initials": "G", "orcid": "0000-0001-6583-3829", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bdb2b7dcd8a4fa497748ee5e165f11e.json"}}, {"family": "Kretzschmar", "given": "Warren W", "initials": "WW", "orcid": "0000-0002-2575-0807", "researcher": {"href": "https://publications.scilifelab.se/researcher/a67389ef276a47cfacec7cbe50da37a7.json"}}, {"family": "Bj\u00f6rklund", "given": "Ann-Charlotte", "initials": "AC", "orcid": "0009-0008-3745-503X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a03cc050a5d446ca3872007f15db3d3.json"}}, {"family": "Creignou", "given": "Maria", "initials": "M", "orcid": "0000-0002-7629-0871", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7d3e87602e943a296e10038400ff2dc.json"}}, {"family": "Hagemann-Jensen", "given": "Michael", "initials": "M", "orcid": "0000-0002-6423-8216", "researcher": {"href": "https://publications.scilifelab.se/researcher/26cb45960bd042c498f4914a342312a0.json"}}, {"family": "Ziegenhain", "given": "Christoph", "initials": "C", "orcid": "0000-0003-2208-4877", "researcher": {"href": "https://publications.scilifelab.se/researcher/3297f21f1a174cd388ac586eda2b5177.json"}}, {"family": "Cabrerizo Granados", "given": "David", "initials": "D", "orcid": "0000-0001-5719-7287", "researcher": {"href": "https://publications.scilifelab.se/researcher/610eac412b5a4527b11776794607930f.json"}}, {"family": "Barbosa", "given": "Indira", "initials": "I", "orcid": "0009-0004-1171-2932", "researcher": {"href": "https://publications.scilifelab.se/researcher/20efd8770db84811a240a8bb70c43939.json"}}, {"family": "Walldin", "given": "Gunilla", "initials": "G", "orcid": "0009-0005-6663-6540", "researcher": {"href": "https://publications.scilifelab.se/researcher/24fb888d0212421eaa2353ed6cc31ac7.json"}}, {"family": "Jansson", "given": "Monika", "initials": "M", "orcid": "0000-0002-9257-0873", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccbf1b2b281742feba0dbd215b6f3228.json"}}, {"family": "Ashley", "given": "Neil", "initials": "N", "orcid": "0000-0002-1655-5137", "researcher": {"href": "https://publications.scilifelab.se/researcher/db3c5c75f5684026a6e267a664c8da99.json"}}, {"family": "Mead", "given": "Adam J", "initials": "AJ", "orcid": "0000-0001-8522-1002", "researcher": {"href": "https://publications.scilifelab.se/researcher/8409c8c7eb604ece9e2ea80ee419336a.json"}}, {"family": "Lundin", "given": "Vanessa", "initials": "V", "orcid": "0000-0003-2335-3370", "researcher": {"href": "https://publications.scilifelab.se/researcher/4648601ee2b74061aadb746516203707.json"}}, {"family": "Dimitriou", "given": "Marios", "initials": "M", "orcid": "0000-0001-8362-2099", "researcher": {"href": "https://publications.scilifelab.se/researcher/531c153359bb400fb48c7324a3bd69ad.json"}}, {"family": "Yoshizato", "given": "Tetsuichi", "initials": "T", "orcid": "0000-0003-4283-2983", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6f499e339d2444b817a81ab2712b9e5.json"}}, {"family": "Woll", "given": "Petter S", "initials": "PS", "orcid": "0000-0002-2340-2526", "researcher": {"href": "https://publications.scilifelab.se/researcher/77ae0c1d2cf5461894c6d0d80ed42f68.json"}}, {"family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}}, {"family": "Sandberg", "given": "Rickard", "initials": "R", "orcid": "0000-0001-6473-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/048c7c9b9edb4366bac7873daad461cd.json"}}, {"family": "Jacobsen", "given": "Sten Eirik W", "initials": "SEW", "orcid": "0000-0002-1362-3659", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fc5e4f49e4330b095c26cd965cc98.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E", "orcid": "0000-0002-7839-3743", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bf8d52e24234fa8b348ad08f58d1d48.json"}}], "type": "journal article", "published": "2024-01-16", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "84", "issue": "2", "pages": "211-225", "issn-l": "0008-5472"}, "abstract": "Myelodysplastic syndromes with ring sideroblasts (MDS-RS) commonly develop from hematopoietic stem cells (HSC) bearing mutations in the splicing factor SF3B1 (SF3B1mt). Direct studies into MDS-RS pathobiology have been limited by a lack of model systems that fully recapitulate erythroid biology and RS development and the inability to isolate viable human RS. Here, we combined successful direct RS isolation from patient samples, high-throughput multiomics analysis of cells encompassing the SF3B1mt stem-erythroid continuum, and functional assays to investigate the impact of SF3B1mt on erythropoiesis and RS accumulation. The isolated RS differentiated, egressed into the blood, escaped traditional nonsense-mediated decay (NMD) mechanisms, and leveraged stress-survival pathways that hinder wild-type hematopoiesis through pathogenic GDF15 overexpression. Importantly, RS constituted a contaminant of magnetically enriched CD34+ cells, skewing bulk transcriptomic data. Mis-splicing in SF3B1mt cells was intensified by erythroid differentiation through accelerated RNA splicing and decreased NMD activity, and SF3B1mt led to truncations in several MDS-implicated genes. Finally, RNA mis-splicing induced an uncoupling of RNA and protein expression, leading to critical abnormalities in proapoptotic p53 pathway genes. Overall, this characterization of erythropoiesis in SF3B1mt RS provides a resource for studying MDS-RS and uncovers insights into the unexpectedly active biology of the \"dead-end\" RS.\n\nRing sideroblast isolation combined with state-of-the-art multiomics identifies survival mechanisms underlying SF3B1-mutant erythropoiesis and establishes an active role for erythroid differentiation and ring sideroblasts themselves in SF3B1-mutant myelodysplastic syndrome pathogenesis.", "doi": "10.1158/0008-5472.CAN-23-3038", "pmid": "37921711", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10790130"}, {"db": "pii", "key": "730004"}], "notes": [], "created": "2024-03-14T11:43:21.354Z", "modified": "2025-02-28T14:21:18.908Z"}, {"entity": "publication", "iuid": "db63a20fea9842658bfd8d977aa1eb42", "links": {"self": {"href": "https://publications.scilifelab.se/publication/db63a20fea9842658bfd8d977aa1eb42.json"}, "display": {"href": "https://publications.scilifelab.se/publication/db63a20fea9842658bfd8d977aa1eb42"}}, "title": "Abstract 3778: Genome-Scale CRISPRa and CRISPRi screening for lncRNA drivers of prostate cancer progression", "authors": [{"family": "Weiss", "given": "Simone", "initials": "S", "orcid": "0000-0002-3553-4315", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a7c021b692c4fc1b2468c63fd0b2c43.json"}}, {"family": "Lord", "given": "Allegra", "initials": "A"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Rovsing", "given": "Anne B", "initials": "AB"}, {"family": "Thomsen", "given": "Emil A", "initials": "EA"}, {"family": "Mikkelsen", "given": "Jacob G", "initials": "JG"}, {"family": "Ulh\u00f8i", "given": "Benedicte", "initials": "B"}, {"family": "Pedersen", "given": "Jakob S", "initials": "JS"}, {"family": "Borre", "given": "Michael", "initials": "M"}, {"family": "S\u00f8rensen", "given": "Karina D", "initials": "KD"}], "type": "journal-article", "published": "2023-04-04", "journal": {"issn": "1538-7445", "volume": "83", "issue": "7_Supplement", "pages": "3778-3778", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": null, "doi": "10.1158/1538-7445.am2023-3778", "pmid": null, "labels": {"CRISPR Functional Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2024-10-02T06:47:38.483Z", "modified": "2025-12-08T10:35:53.489Z"}, {"entity": "publication", "iuid": "55a7aa6ba5f64d12b7d237818bdde3e7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/55a7aa6ba5f64d12b7d237818bdde3e7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/55a7aa6ba5f64d12b7d237818bdde3e7"}}, "title": "Abstract A007: Pancreatic cancer comprises co-existing transcriptional states regulated by distinct master regulator programs", "authors": [{"family": "Laise", "given": "Pasquale", "initials": "P", "orcid": "0000-0003-1469-4704", "researcher": {"href": "https://publications.scilifelab.se/researcher/0592a382bfcf4f2d83e5d79f89bb425a.json"}}, {"family": "Turunen", "given": "Mikko", "initials": "M", "orcid": "0000-0001-5134-1559", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6f360468c4f4329b59de43f4d8eff27.json"}}, {"family": "Maurer", "given": "Hans Carlo", "initials": "HC", "orcid": "0000-0002-2193-6014", "researcher": {"href": "https://publications.scilifelab.se/researcher/48cde5fef80c4b0e917707ba825b8143.json"}}, {"family": "Garcia", "given": "Alvaro Curiel", "initials": "AC"}, {"family": "Elyada", "given": "Ela", "initials": "E"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Tomassoni", "given": "Lorenzo", "initials": "L"}, {"family": "Worley", "given": "Jeremy", "initials": "J", "orcid": "0000-0003-4517-7080", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba8e8bccdd304afe8ac772f533c75e09.json"}}, {"family": "Alvarez", "given": "Mariano J", "initials": "MJ", "orcid": "0000-0002-7503-2491", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c7e5b525ad44f4859b434c85ebe066.json"}}, {"family": "Kesner", "given": "Jordan", "initials": "J"}, {"family": "Tan", "given": "Xiangtian", "initials": "X"}, {"family": "Tagore", "given": "Somnath", "initials": "S", "orcid": "0000-0003-4742-3679", "researcher": {"href": "https://publications.scilifelab.se/researcher/4aeec80fda63405eaab09827e3f9b704.json"}}, {"family": "Fernandez", "given": "Ester Calvo", "initials": "EC"}, {"family": "Wong", "given": "Kelly", "initials": "K"}, {"family": "Wang", "given": "Alexander L E", "initials": "ALE"}, {"family": "Ge", "given": "Sabrina", "initials": "S"}, {"family": "Iuga", "given": "Alina C", "initials": "AC"}, {"family": "Griffin", "given": "Aaron T", "initials": "AT"}, {"family": "Wong", "given": "Winston", "initials": "W"}, {"family": "Manji", "given": "Gulam A", "initials": "GA"}, {"family": "Notta", "given": "Faiyaz", "initials": "F", "orcid": "0000-0002-5748-3985", "researcher": {"href": "https://publications.scilifelab.se/researcher/82840ed4e5294488bc9732dcd4fdc36c.json"}}, {"family": "Tuveson", "given": "David A", "initials": "DA"}, {"family": "Olive", "given": "Kenneth P P", "initials": "KPP"}, {"family": "Califano", "given": "Andrea", "initials": "A"}], "type": "journal-article", "published": "2022-11-15", "journal": {"issn": "1538-7445", "volume": "82", "issue": "22_Supplement", "pages": "A007-A007", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": null, "doi": "10.1158/1538-7445.panca22-a007", "pmid": null, "labels": {"CRISPR Functional Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2024-10-02T06:48:10.186Z", "modified": "2025-12-08T10:36:02.929Z"}, {"entity": "publication", "iuid": "af444c3012184e0887f12a8f83b56952", "links": {"self": {"href": "https://publications.scilifelab.se/publication/af444c3012184e0887f12a8f83b56952.json"}, "display": {"href": "https://publications.scilifelab.se/publication/af444c3012184e0887f12a8f83b56952"}}, "title": "Dormant SOX9-positive cells facilitate MYC-driven recurrence of medulloblastoma.", "authors": [{"family": "Borgenvik", "given": "Anna", "initials": "A", "orcid": "0000-0003-4696-7703", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a6b1da64eeb459092d6f32823d474ba.json"}}, {"family": "Holmberg", "given": "Karl O", "initials": "KO", "orcid": "0000-0002-4402-0586", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b44ff77230e492bb0630372281a432c.json"}}, {"family": "Bolin", "given": "Sara", "initials": "S", "orcid": "0000-0003-2835-1518", "researcher": {"href": "https://publications.scilifelab.se/researcher/8d4cf00b336942638b1b06bb8a3e95f8.json"}}, {"family": "Zhao", "given": "Miao", "initials": "M", "orcid": "0000-0002-4895-1177", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9c4e2515b414dee94aaeca71569699b.json"}}, {"family": "Savov", "given": "Vasil", "initials": "V", "orcid": "0000-0003-2347-1975", "researcher": {"href": "https://publications.scilifelab.se/researcher/326ce1c1944c4217bcdf25520774d403.json"}}, {"family": "Ros\u00e9n", "given": "Gabriela", "initials": "G", "orcid": "0000-0002-7762-1468", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f652227f9c147f082404e42d4b06e76.json"}}, {"family": "Hutter", "given": "Sonja", "initials": "S", "orcid": "0000-0003-3340-9315", "researcher": {"href": "https://publications.scilifelab.se/researcher/b75be5efd15d4575a6d8b70a3d08ee7d.json"}}, {"family": "Garancher", "given": "Alexandra", "initials": "A", "orcid": "0000-0001-5779-2860", "researcher": {"href": "https://publications.scilifelab.se/researcher/80409227c84144c2b287efe12d6adbeb.json"}}, {"family": "Suryo Rahmanto", "given": "Aldwin", "initials": "A", "orcid": "0000-0002-4593-286X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6e9bc6bf4684bb2bd6a299cd475d4fa.json"}}, {"family": "Bergstr\u00f6m", "given": "Tobias", "initials": "T", "orcid": "0000-0002-4557-2390", "researcher": {"href": "https://publications.scilifelab.se/researcher/170dee5895114905a47f673c23bc27c5.json"}}, {"family": "Olsen", "given": "Thale Kristin", "initials": "TK", "orcid": "0000-0003-4655-7384", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa772bafc60a42f7a4e24b724b9dd529.json"}}, {"family": "Mainwaring", "given": "Oliver J", "initials": "OJ", "orcid": "0000-0002-7973-9849", "researcher": {"href": "https://publications.scilifelab.se/researcher/494a0479041f41149902feb34f668043.json"}}, {"family": "Sattanino", "given": "Damiana", "initials": "D", "orcid": "0000-0002-2747-4842", "researcher": {"href": "https://publications.scilifelab.se/researcher/f76c1d5a46fa446b928e1bacb1e2f81b.json"}}, {"family": "Verbaan", "given": "Annemieke D", "initials": "AD", "orcid": "0000-0001-6793-0577", "researcher": {"href": "https://publications.scilifelab.se/researcher/38f656179a264c8baf3f7515fc642ee0.json"}}, {"family": "Rusert", "given": "Jessica M", "initials": "JM", "orcid": "0000-0003-0751-2693", "researcher": {"href": "https://publications.scilifelab.se/researcher/68b9b78643ed4cf686a48177971def24.json"}}, {"family": "Sundstrom", "given": "Anders", "initials": "A", "orcid": "0000-0003-3942-6271", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cf009de33e547aa9f850ac18c2a0c32.json"}}, {"family": "Ballester Bravo", "given": "Mar", "initials": "M", "orcid": "0000-0002-1371-6679", "researcher": {"href": "https://publications.scilifelab.se/researcher/a54bfd8cca5d472f9917bcb7d75f98fd.json"}}, {"family": "Dang", "given": "Yonglong", "initials": "Y", "orcid": "0000-0001-9705-5507", "researcher": {"href": "https://publications.scilifelab.se/researcher/be8f706e753a4d10ba4ee5f3aef6fc6b.json"}}, {"family": "Wenz", "given": "Amelie S", "initials": "AS", "orcid": "0000-0003-1929-382X", "researcher": {"href": "https://publications.scilifelab.se/researcher/113e59df51d0438c90dfef742c67fead.json"}}, {"family": "Richardson", "given": "Stacey", "initials": "S", "orcid": "0000-0003-1841-6330", "researcher": {"href": "https://publications.scilifelab.se/researcher/89ecfd4f24154b6eb4ac6befcc72ae35.json"}}, {"family": "Fotaki", "given": "Grammatiki", "initials": "G", "orcid": "0000-0002-1343-1921", "researcher": {"href": "https://publications.scilifelab.se/researcher/65f67224986646d3a74b6733253ec0a1.json"}}, {"family": "Hill", "given": "Rebecca M", "initials": "RM", "orcid": "0000-0001-8405-2219", "researcher": {"href": "https://publications.scilifelab.se/researcher/59da56669a874fa5af8c3009595c1190.json"}}, {"family": "Dubuc", "given": "Adrian M", "initials": "AM", "orcid": "0000-0002-3447-6715", "researcher": {"href": "https://publications.scilifelab.se/researcher/4df0a67f53ac4fb3b62bc35e06bb6d7c.json"}}, {"family": "Kalushkova", "given": "Antonia", "initials": "A", "orcid": "0000-0003-4535-506X", "researcher": {"href": "https://publications.scilifelab.se/researcher/df89c7522b7b4af3b3cef8555380fe8c.json"}}, {"family": "Remke", "given": "Marc", "initials": "M", "orcid": "0000-0002-9404-9993", "researcher": {"href": "https://publications.scilifelab.se/researcher/8de3293b14654714a490ad3c1ebacdb9.json"}}, {"family": "Cancer", "given": "Matko", "initials": "M", "orcid": "0000-0001-5825-5151", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a428908f080488a990cef0ce873e17d.json"}}, {"family": "Jernberg-Wiklund", "given": "Helena", "initials": "H", "orcid": "0000-0002-9319-7986", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc67ebc79ba54e0aa635f58641533f0e.json"}}, {"family": "Giraud", "given": "G\u00e9raldine", "initials": "G", "orcid": "0000-0002-2771-9889", "researcher": {"href": "https://publications.scilifelab.se/researcher/802841f141834cf28283e925f9e08b54.json"}}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-5657-2839", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef7ddc09e57745909175e41ac2d1b647.json"}}, {"family": "Taylor", "given": "Michael D", "initials": "MD", "orcid": "0000-0001-7009-3466", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ed8b81b674444bdb45e080ec459252f.json"}}, {"family": "Sangfelt", "given": "Olle", "initials": "O", "orcid": "0000-0002-0316-0195", "researcher": {"href": "https://publications.scilifelab.se/researcher/2cd4756206314abf9e23caca719b70ec.json"}}, {"family": "Clifford", "given": "Steven C", "initials": "SC", "orcid": "0000-0003-4893-2184", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed4d6271609e412a9c57bc3206b17c1f.json"}}, {"family": "Schuller", "given": "Ulrich", "initials": "U", "orcid": "0000-0002-8731-1121", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8e5ba2ee7244467b78a810618ee055d.json"}}, {"family": "Wechsler-Reya", "given": "Robert J", "initials": "RJ", "orcid": "0000-0002-7463-8352", "researcher": {"href": "https://publications.scilifelab.se/researcher/25ca624b1ebd4fae9533cb83e8df3804.json"}}, {"family": "Weishaupt", "given": "Holger", "initials": "H", "orcid": "0000-0002-0364-2709", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f48d0ba4ee14f1eb17f1597d3aa70e5.json"}}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications.scilifelab.se/researcher/69679cebbc90496f9c5b32f56d966654.json"}}], "type": "journal article", "published": "2022-10-11", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "issn-l": "0008-5472", "volume": null, "issue": null, "pages": null}, "abstract": "Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, while MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.", "doi": "10.1158/0008-5472.CAN-22-2108", "pmid": "36219398", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI Single cell": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "709709"}], "notes": [], "created": "2022-11-29T09:32:14.890Z", "modified": "2024-01-16T13:48:34.774Z"}, {"entity": "publication", "iuid": "f35cccb3c5f4472e8b873c19f7a4d019", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f35cccb3c5f4472e8b873c19f7a4d019.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f35cccb3c5f4472e8b873c19f7a4d019"}}, "title": "CRISPR/Cas9-Induced DNA Damage Enriches for Mutations in a p53-Linked Interactome: Implications for CRISPR-Based Therapies.", "authors": [{"family": "Jiang", "given": "Long", "initials": "L", "orcid": "0000-0002-8720-8992", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d46414099a14d3ba156b86e18ff9a97.json"}}, {"family": "Ingelshed", "given": "Katrine", "initials": "K"}, {"family": "Shen", "given": "Yunbing", "initials": "Y", "orcid": "0000-0001-7711-5576", "researcher": {"href": "https://publications.scilifelab.se/researcher/4738c4888806400c855c6d41acad55c3.json"}}, {"family": "Boddul", "given": "Sanjaykumar V", "initials": "SV"}, {"family": "Iyer", "given": "Vaishnavi Srinivasan", "initials": "VS", "orcid": "0000-0003-1083-8950", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7996e23c41440c1a214869af40387ba.json"}}, {"family": "Kasza", "given": "Zsolt", "initials": "Z", "orcid": "0000-0003-0884-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5e6174fb42b452ba8543e5c7ca0b179.json"}}, {"family": "Sedimbi", "given": "Saikiran", "initials": "S", "orcid": "0000-0001-5243-8395", "researcher": {"href": "https://publications.scilifelab.se/researcher/992fbe2e1e6e49fc81cfadf2ab89ed8e.json"}}, {"family": "Lane", "given": "David P", "initials": "DP"}, {"family": "Wermeling", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-9633-677X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a34df8186ba24df3b14fe9743cf546b4.json"}}], "type": "journal article", "published": "2022-01-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "82", "issue": "1", "pages": "36-45", "issn-l": "0008-5472"}, "abstract": "Inactivating p53 mutations are the most abundant genetic alterations found in cancer. Here we show that CRISPR/Cas9-induced double-stranded DNA breaks enrich for cells deficient in p53 and in genes of a core CRISPR-p53 tumor suppressor interactome. Such enrichment could predispose to cancer development and thus pose a challenge for clinical CRISPR use. Transient p53 inhibition could suppress the enrichment of cells with these mutations. The level of DNA damage response induced by an sgRNA influenced the enrichment of p53-deficient cells and could be a relevant parameter in sgRNA design to limit cellular enrichment. Furthermore, a dataset of >800 human cancer cell lines identified additional factors influencing the enrichment of p53-mutated cells, including strong baseline CDKN1A expression as a predictor for an active CRISPR-p53 axis. Taken together, these data provide details about p53 biology in the context of CRISPR-induced DNA damage and identify strategies to enable safer CRISPR use. SIGNIFICANCE: CRISPR-mediated DNA damage enriches for cells with escape mutations in a core CRISPR-p53 interactome, which can be suppressed by transient inhibition of p53.", "doi": "10.1158/0008-5472.CAN-21-1692", "pmid": "34750099", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-21-1692"}], "notes": [], "created": "2022-11-09T15:57:00.205Z", "modified": "2024-01-16T13:48:37.858Z"}, {"entity": "publication", "iuid": "9acd4142dc314a259044f6bf390a903b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9acd4142dc314a259044f6bf390a903b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9acd4142dc314a259044f6bf390a903b"}}, "title": "MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.", "authors": [{"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Calder\u00f3n-Monta\u00f1o", "given": "Jos\u00e9 Manuel", "initials": "JM", "orcid": "0000-0001-6845-797X", "researcher": {"href": "https://publications.scilifelab.se/researcher/474af64ef5914eb7b99f9d98bf9a7455.json"}}, {"family": "Pham", "given": "Therese M", "initials": "TM"}, {"family": "Erkers", "given": "Tom", "initials": "T"}, {"family": "Tsuber", "given": "Viktoriia", "initials": "V"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "H\u00f6glund", "given": "Andreas", "initials": "A"}, {"family": "Heshmati", "given": "Yaser", "initials": "Y"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B", "orcid": "0000-0001-8658-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/4645bc97a8024c548111802101b83571.json"}}, {"family": "Nagesh Danda", "given": "Akhilesh", "initials": "A"}, {"family": "Gad", "given": "Helge", "initials": "H", "orcid": "0000-0001-6530-1443", "researcher": {"href": "https://publications.scilifelab.se/researcher/6273ef3dd1574185af0a83e9ab31bfe5.json"}}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "G\u00f6kt\u00fcrk", "given": "Camilla", "initials": "C", "orcid": "0000-0002-6272-9927", "researcher": {"href": "https://publications.scilifelab.se/researcher/9318cec5020f4c92b8393b20242c0d58.json"}}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Friedrich", "given": "Stefanie", "initials": "S", "orcid": "0000-0002-3889-5589", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e1de4177ae649aba93a633ca451ebdb.json"}}, {"family": "Centio", "given": "Anders", "initials": "A"}, {"family": "Estruch", "given": "Montserrat", "initials": "M", "orcid": "0000-0002-7162-4158", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf0c60406fc74282b87f74170571d297.json"}}, {"family": "V\u00e5tsveen", "given": "Thea Kristin", "initials": "TK"}, {"family": "Struyf", "given": "Nona", "initials": "N", "orcid": "0000-0002-6975-0753", "researcher": {"href": "https://publications.scilifelab.se/researcher/1295c3be31024c4fa2da10cffe42c406.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Wallner", "given": "Olov", "initials": "O"}, {"family": "Sandvall", "given": "Teresa", "initials": "T"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}, {"family": "Theilgaard-M\u00f6nch", "given": "Kim", "initials": "K", "orcid": "0000-0002-4239-4939", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ac2392d2c784203b15e8ec53d6a746e.json"}}, {"family": "Garnett", "given": "Mathew J", "initials": "MJ", "orcid": "0000-0002-2618-4237", "researcher": {"href": "https://publications.scilifelab.se/researcher/81268f585935408e9a9673db9da394f6.json"}}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Walfridsson", "given": "Julian", "initials": "J"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74c79d4b11346a4918f536b5a678e12.json"}}], "type": "journal article", "published": "2021-11-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "81", "issue": "22", "pages": "5733-5744", "issn-l": "0008-5472"}, "abstract": "Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin-CD34+CD38-), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial. SIGNIFICANCE: The MTH1 inhibitor TH1579 is a potential novel AML treatment, targeting both blasts and the pivotal leukemic stem cells while sparing normal bone marrow cells.", "doi": "10.1158/0008-5472.CAN-21-0061", "pmid": "34593524", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9397639"}, {"db": "pii", "key": "0008-5472.CAN-21-0061"}], "notes": [], "created": "2023-11-27T21:58:04.269Z", "modified": "2024-01-16T13:48:38.121Z"}, {"entity": "publication", "iuid": "a51b82e8fc3f416ba97747c09e057418", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a51b82e8fc3f416ba97747c09e057418.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a51b82e8fc3f416ba97747c09e057418"}}, "title": "Subcellular Distribution of p53 by the p53-Responsive lncRNA NBAT1 Determines Chemotherapeutic Response in Neuroblastoma.", "authors": [{"family": "Mitra", "given": "Sanhita", "initials": "S"}, {"family": "Muralidharan", "given": "Somsundar Veppil", "initials": "SV", "orcid": "0000-0002-5563-2879", "researcher": {"href": "https://publications.scilifelab.se/researcher/a80c5092c17a4f1ea628b014855ad5f7.json"}}, {"family": "Di Marco", "given": "Mirco", "initials": "M"}, {"family": "Juvvuna", "given": "Prasanna Kumar", "initials": "PK", "orcid": "0000-0003-4296-9621", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6eb04008a0c490a9b119338855092d0.json"}}, {"family": "Kosalai", "given": "Subazini Thankaswamy", "initials": "ST"}, {"family": "Reischl", "given": "Silke", "initials": "S"}, {"family": "Jachimowicz", "given": "Daniel", "initials": "D"}, {"family": "Subhash", "given": "Santhilal", "initials": "S", "orcid": "0000-0002-0077-4597", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ca22115b7c9444ab2056126a1c9d36d.json"}}, {"family": "Raimondi", "given": "Ivan", "initials": "I"}, {"family": "Kurian", "given": "Leo", "initials": "L"}, {"family": "Huarte", "given": "Maite", "initials": "M"}, {"family": "Kogner", "given": "Per", "initials": "P", "orcid": "0000-0002-2202-9694", "researcher": {"href": "https://publications.scilifelab.se/researcher/e963274b921a4a2c8263f509334d4e22.json"}}, {"family": "Fischer", "given": "Matthias", "initials": "M"}, {"family": "Johnsen", "given": "John Inge", "initials": "JI", "orcid": "0000-0003-1277-812X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c5b7b4c780349afacf3063e311c334e.json"}}, {"family": "Mondal", "given": "Tanmoy", "initials": "T"}, {"family": "Kanduri", "given": "Chandrasekhar", "initials": "C"}], "type": "journal article", "published": "2021-03-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "81", "issue": "6", "pages": "1457-1471", "issn-l": "0008-5472"}, "abstract": "Neuroblastoma has a low mutation rate for the p53 gene. Alternative ways of p53 inactivation have been proposed in neuroblastoma, such as abnormal cytoplasmic accumulation of wild-type p53. However, mechanisms leading to p53 inactivation via cytoplasmic accumulation are not well investigated. Here we show that the neuroblastoma risk-associated locus 6p22.3-derived tumor suppressor NBAT1 is a p53-responsive lncRNA that regulates p53 subcellular levels. Low expression of NBAT1 provided resistance to genotoxic drugs by promoting p53 accumulation in cytoplasm and loss from mitochondrial and nuclear compartments. Depletion of NBAT1 altered CRM1 function and contributed to the loss of p53-dependent nuclear gene expression during genotoxic drug treatment. CRM1 inhibition rescued p53-dependent nuclear functions and sensitized NBAT1-depleted cells to genotoxic drugs. Combined inhibition of CRM1 and MDM2 was even more effective in sensitizing aggressive neuroblastoma cells with p53 cytoplasmic accumulation. Thus, our mechanistic studies uncover an NBAT1-dependent CRM1/MDM2-based potential combination therapy for patients with high-risk neuroblastoma. SIGNIFICANCE: This study shows how a p53-responsive lncRNA mediates chemotherapeutic response by modulating nuclear p53 pathways and identifies a potential treatment strategy for patients with high-risk neuroblastoma.", "doi": "10.1158/0008-5472.CAN-19-3499", "pmid": "33372039", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-3499"}], "notes": [], "created": "2022-11-09T15:47:31.560Z", "modified": "2024-01-16T13:48:40.460Z"}, {"entity": "publication", "iuid": "493e83237a904012b71fd863f7f57aa6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/493e83237a904012b71fd863f7f57aa6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/493e83237a904012b71fd863f7f57aa6"}}, "title": "Time-Dependent Effects of Oral Contraceptive Use on Breast, Ovarian, and Endometrial Cancers.", "authors": [{"family": "Karlsson", "given": "Torgny", "initials": "T"}, {"family": "Johansson", "given": "Therese", "initials": "T"}, {"family": "H\u00f6glund", "given": "Julia", "initials": "J"}, {"family": "Ek", "given": "Weronica E", "initials": "WE"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5"}], "type": "journal article", "published": "2021-02-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "81", "issue": "4", "pages": "1153-1162", "issn-l": "0008-5472"}, "abstract": "Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose of this study is to clarify the time-dependent effects between long-term oral contraceptive use and cancer risk. We performed an observational study in 256,661 women from UK Biobank, born between 1939 and 1970. Information on cancer diagnoses were collected from self-reported data and from national registers until March 2019. Cumulative risk of cancer over the timespan of the study, as measured by the OR, and instantaneous risk, as measured by the HR, were assessed using Logistic and Cox regression analyses, respectively. The odds were lower among ever users, compared with never users, for ovarian cancer [OR = 0.72; 95% confidence interval (CI), 0.65-0.81] and endometrial cancer (OR = 0.68; 95% CI, 0.62-0.75), an association that was stronger with longer use (P < 0.001). Increased odds were seen for breast cancer in women when limiting the follow-up to 55 years of age (OR = 1.10; 95% CI, 1.03-1.17), but not for the full timespan. We only found a higher HR for breast cancer in former users immediately (\u22642 years) after discontinued oral contraceptive use (HR = 1.55; 95% CI, 1.06-2.28), whereas the protective association for ovarian and endometrial cancer remained significant up to 35 years after last use of oral contraceptives. Given the body of evidence presented in our study, we argue that oral contraceptives can dramatically reduce women's risk of ovarian and endometrial cancer, whereas their effect on lifetime risk of breast cancer is limited. SIGNIFICANCE: These results enable women and physicians to make more informed decisions considering oral contraceptive use, thus constituting an important step toward personalized medicine.", "doi": "10.1158/0008-5472.CAN-20-2476", "pmid": "33334812", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-20-2476"}], "notes": [], "created": "2022-11-09T15:42:09.563Z", "modified": "2024-01-16T13:48:40.679Z"}, {"entity": "publication", "iuid": "3c85b2fe425e40f7816b5c4810c0231e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c85b2fe425e40f7816b5c4810c0231e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c85b2fe425e40f7816b5c4810c0231e"}}, "title": "Fulvestrant-Mediated Attenuation of the Innate Immune Response Decreases ER+ Breast Cancer Growth In Vivo More Effectively than Tamoxifen.", "authors": [{"family": "Abrahamsson", "given": "Annelie", "initials": "A", "orcid": "0000-0002-6791-7951", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a5b588a24b495fabdc337c10f69f59.json"}}, {"family": "Rodriguez", "given": "Gabriela Vazquez", "initials": "GV", "orcid": "0000-0001-9310-2433", "researcher": {"href": "https://publications.scilifelab.se/researcher/3af0ed418b6e4b0ab26565a4b1e7a033.json"}}, {"family": "Dabrosin", "given": "Charlotta", "initials": "C", "orcid": "0000-0001-7191-0018", "researcher": {"href": "https://publications.scilifelab.se/researcher/66c887621cb84be4a4bc1c4cfb4c86de.json"}}], "type": "journal article", "published": "2020-10-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "20", "pages": "4487-4499", "issn-l": "0008-5472"}, "abstract": "Although blocking estrogen-dependent signaling is a cornerstone of adjuvant treatment for breast cancer, 25% of patients experience recurrent disease. Stroma events including innate immune responses are key in cancer progression. How different estrogen receptor (ER)-targeting therapies, including the partial agonist tamoxifen and the pure antagonist fulvestrant, affect the tumor stroma has not yet been elucidated. Fulvestrant is used in only postmenopausal patients, and its effects in the presence of estradiol remain undetermined. Here we observe that fulvestrant decreases ER+ breast cancer growth compared with tamoxifen in the presence of physiologic levels of estradiol in human breast cancer in nude mice and in murine breast cancer in immune-competent mice. Fulvestrant significantly inhibited macrophage and neutrophil infiltration in both models. These effects were corroborated in a zebrafish model where fulvestrant inhibited neutrophil- and macrophage-dependent cancer cell dissemination more effectively than tamoxifen. A comprehensive analysis of 234 human proteins released into the cancer microenvironment by the cancer cells sampled via microdialysis in vivo revealed that 38 proteins were altered following both treatments; 25 of these proteins were associated with immune response and were altered by fulvestrant only. Compared with tamoxifen, fulvestrant significantly affected inflammatory proteins released by murine stroma cells. Importantly, in vivo microdialysis of human ER+ breast cancer revealed that the majority of affected proteins in murine models were upregulated in patients. Together, these results suggest that fulvestrant targets ER+ breast cancer more effectively than tamoxifen even in the presence of estradiol, mainly by attenuation of the innate immune response. SIGNIFICANCE: These findings demonstrate novel effects of the pure antiestrogen fulvestrant in ER+ breast cancer and evaluate its effects under physiologic levels of estradiol, representative of premenopausal patients.", "doi": "10.1158/0008-5472.CAN-20-1705", "pmid": "32855207", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-20-1705"}], "notes": [], "created": "2020-09-15T07:21:32.922Z", "modified": "2021-11-10T12:47:55.756Z"}, {"entity": "publication", "iuid": "80af4f01148941ee84d283dbe27a5578", "links": {"self": {"href": "https://publications.scilifelab.se/publication/80af4f01148941ee84d283dbe27a5578.json"}, "display": {"href": "https://publications.scilifelab.se/publication/80af4f01148941ee84d283dbe27a5578"}}, "title": "Platelet-Specific PDGFB Ablation Impairs Tumor Vessel Integrity and Promotes Metastasis.", "authors": [{"family": "Zhang", "given": "Yanyu", "initials": "Y"}, {"family": "Cedervall", "given": "Jessica", "initials": "J"}, {"family": "Hamidi", "given": "Anahita", "initials": "A", "orcid": "0000-0002-5445-2446", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb5b0682d0bc4c2aae58ee0b20329da8.json"}}, {"family": "Herre", "given": "Melanie", "initials": "M"}, {"family": "Viitaniemi", "given": "Kati", "initials": "K"}, {"family": "D'Amico", "given": "Gabriela", "initials": "G"}, {"family": "Miao", "given": "Zuoxiu", "initials": "Z"}, {"family": "Unnithan", "given": "Ragaseema Valsala Madhavan", "initials": "RVM", "orcid": "0000-0002-5915-1685", "researcher": {"href": "https://publications.scilifelab.se/researcher/64fc9f8e946e4e50bb181c5048e7f364.json"}}, {"family": "Vaccaro", "given": "Alessandra", "initials": "A"}, {"family": "van Hooren", "given": "Luuk", "initials": "L"}, {"family": "Georganaki", "given": "Maria", "initials": "M"}, {"family": "Thulin", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Qiao", "given": "Qi", "initials": "Q"}, {"family": "Andrae", "given": "Johanna", "initials": "J"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Alitalo", "given": "Kari", "initials": "K"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}, {"family": "Dimberg", "given": "Anna", "initials": "A"}, {"family": "Olsson", "given": "Anna-Karin", "initials": "AK"}], "type": "journal article", "published": "2020-08-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "16", "pages": "3345-3358", "issn-l": "0008-5472"}, "abstract": "Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor \u03b2-positive pericytes to blood vessels. The endothelium is an essential source of PDGFB in this process. Platelets constitute a major reservoir of PDGFB and are continuously activated in the tumor microenvironment, exposing tumors to the plethora of growth factors contained in platelet granules. Here, we show that tumor vascular function, as well as pericyte coverage is significantly impaired in mice with conditional knockout of PDGFB in platelets. A lack of PDGFB in platelets led to enhanced hypoxia and epithelial-to-mesenchymal transition in the primary tumors, elevated levels of circulating tumor cells, and increased spontaneous metastasis to the liver or lungs in two mouse models. These findings establish a previously unknown role for platelet-derived PDGFB, whereby it promotes and maintains vascular integrity in the tumor microenvironment by contributing to the recruitment of pericytes. SIGNIFICANCE: Conditional knockout of PDGFB in platelets demonstrates its previously unknown role in the maintenance of tumor vascular integrity and host protection against metastasis.", "doi": "10.1158/0008-5472.CAN-19-3533", "pmid": "32586981", "labels": {"PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-3533"}], "notes": [], "created": "2020-08-26T14:42:44.583Z", "modified": "2023-04-14T13:55:52.207Z"}, {"entity": "publication", "iuid": "3d52c9ab12914a419feae20a6e446826", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d52c9ab12914a419feae20a6e446826.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d52c9ab12914a419feae20a6e446826"}}, "title": "Thermal Proteome Profiling Identifies Oxidative-Dependent Inhibition of the Transcription of Major Oncogenes as a New Therapeutic Mechanism for Select Anticancer Compounds.", "authors": [{"family": "Peuget", "given": "Sylvain", "initials": "S"}, {"family": "Zhu", "given": "Jiawei", "initials": "J"}, {"family": "Sanz", "given": "Gema", "initials": "G", "orcid": "0000-0002-6227-0431", "researcher": {"href": "https://publications.scilifelab.se/researcher/3353dc98689341b4824217786d1e3956.json"}}, {"family": "Singh", "given": "Madhurendra", "initials": "M"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Chen", "given": "Xinsong", "initials": "X"}, {"family": "Shi", "given": "Yao", "initials": "Y"}, {"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Rihani", "given": "Ali", "initials": "A", "orcid": "0000-0002-6176-0519", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dc94d95e8204181bf3e75354ec1678b.json"}}, {"family": "Moyano-Galceran", "given": "Lidia", "initials": "L", "orcid": "0000-0001-9219-6394", "researcher": {"href": "https://publications.scilifelab.se/researcher/085eed2a15bc4be08acbe21a18cb4e6c.json"}}, {"family": "Carlson", "given": "Joseph W", "initials": "JW", "orcid": "0000-0002-3006-4107", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb81cad4b24d4692bc21bda7305f21f1.json"}}, {"family": "Hjerpe", "given": "Elisabet", "initials": "E"}, {"family": "Joneborg", "given": "Ulrika", "initials": "U"}, {"family": "Lehti", "given": "Kaisa", "initials": "K", "orcid": "0000-0001-9110-8719", "researcher": {"href": "https://publications.scilifelab.se/researcher/480c0e2b92df4dccbae3940721525345.json"}}, {"family": "Hartman", "given": "Johan", "initials": "J", "orcid": "0000-0002-6500-8527", "researcher": {"href": "https://publications.scilifelab.se/researcher/da7cefda6e00463d8ba95fc63eeb8f0a.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Zubarev", "given": "Roman", "initials": "R", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Selivanova", "given": "Galina", "initials": "G"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "issn-l": "0008-5472", "volume": "80", "issue": "7", "pages": "1538-1550"}, "abstract": "Identification of the molecular mechanism of action (MoA) of bioactive compounds is a crucial step for drug development but remains a challenging task despite recent advances in technology. In this study, we applied multidimensional proteomics, sensitivity correlation analysis, and transcriptomics to identify a common MoA for the anticancer compounds RITA, aminoflavone (AF), and oncrasin-1 (Onc-1). Global thermal proteome profiling revealed that the three compounds target mRNA processing and transcription, thereby attacking a cancer vulnerability, transcriptional addiction. This led to the preferential loss of expression of oncogenes involved in PDGF, EGFR, VEGF, insulin/IGF/MAPKK, FGF, Hedgehog, TGF\u03b2, and PI3K signaling pathways. Increased reactive oxygen species level in cancer cells was a prerequisite for targeting the mRNA transcription machinery, thus conferring cancer selectivity to these compounds. Furthermore, DNA repair factors involved in homologous recombination were among the most prominently repressed proteins. In cancer patient samples, RITA, AF, and Onc-1 sensitized to poly(ADP-ribose) polymerase inhibitors both in vitro and ex vivo These findings might pave a way for new synthetic lethal combination therapies.Significance: These findings highlight agents that target transcriptional addiction in cancer cells and suggest combination treatments that target RNA processing and DNA repair pathways simultaneously as effective cancer therapies.", "doi": "10.1158/0008-5472.CAN-19-2069", "pmid": "32019870", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-2069"}], "notes": [], "created": "2020-02-07T22:52:26.989Z", "modified": "2024-01-18T23:48:25.871Z"}, {"entity": "publication", "iuid": "c415e1ad145e4e3980e7a96e3c492895", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c415e1ad145e4e3980e7a96e3c492895.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c415e1ad145e4e3980e7a96e3c492895"}}, "title": "Extensive Clonal Branching Shapes the Evolutionary History of High-Risk Pediatric Cancers.", "authors": [{"family": "Andersson", "given": "Natalie", "initials": "N"}, {"family": "Bakker", "given": "Bjorn", "initials": "B", "orcid": "0000-0003-3095-7287", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2f6637d70ea487bbd752150140416dc.json"}}, {"family": "Karlsson", "given": "Jenny", "initials": "J"}, {"family": "Valind", "given": "Anders", "initials": "A"}, {"family": "Holmquist Mengelbier", "given": "Linda", "initials": "L", "orcid": "0000-0002-3632-2760", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6729b3f10e84432839564c382473607.json"}}, {"family": "Spierings", "given": "Diana C J", "initials": "DCJ", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F"}, {"family": "Gisselsson", "given": "David", "initials": "D"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "7", "pages": "1512-1523", "issn-l": "0008-5472"}, "abstract": "Darwinian evolution of tumor cells remains underexplored in childhood cancer. We here reconstruct the evolutionary histories of 56 pediatric primary tumors, including 24 neuroblastomas, 24 Wilms tumors, and 8 rhabdomyosarcomas. Whole-genome copy-number and whole-exome mutational profiling of multiple regions per tumor were performed, followed by clonal deconvolution to reconstruct a phylogenetic tree for each tumor. Overall, 88% of the tumors exhibited genetic variation among primary tumor regions. This variability typically emerged through collateral phylogenetic branching, leading to spatial variability in the distribution of more than 50% (96/173) of detected diagnostically informative genetic aberrations. Single-cell sequencing of 547 individual cancer cells from eight solid pediatric tumors confirmed branching evolution to be a fundamental underlying principle of genetic variation in all cases. Strikingly, cell-to-cell genetic diversity was almost twice as high in aggressive compared with clinically favorable tumors (median Simpson index of diversity 0.45 vs. 0.88; P = 0.029). Similarly, a comparison of multiregional sampling data from a total of 274 tumor regions showed that new phylogenetic branches emerge at a higher frequency per sample and carry a higher mutational load in high-risk than in low-risk tumors. Timelines based on spatial genetic variation showed that the mutations most influencing relapse risk occur at initiation of clonal expansion in neuroblastoma and rhabdomyosarcoma, whereas in Wilms tumor, they are late events. Thus, from an evolutionary standpoint, some high-risk childhood cancers are born bad, whereas others grow worse over time. SIGNIFICANCE: Different pediatric cancers with a high risk of relapse share a common generic pattern of extensively branching evolution of somatic mutations. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/7/1512/F1.large.jpg.", "doi": "10.1158/0008-5472.CAN-19-3468", "pmid": "32041836", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-3468"}], "notes": [], "created": "2020-07-08T13:05:37.152Z", "modified": "2021-11-10T12:52:26.783Z"}, {"entity": "publication", "iuid": "b672cfafccdb450093604f54c0d0dc48", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b672cfafccdb450093604f54c0d0dc48.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b672cfafccdb450093604f54c0d0dc48"}}, "title": "Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses.", "authors": [{"family": "Niklasson", "given": "Mia", "initials": "M"}, {"family": "Maddalo", "given": "Gianluca", "initials": "G"}, {"family": "Sramkova", "given": "Zuzana", "initials": "Z"}, {"family": "Mutlu", "given": "Ercan", "initials": "E"}, {"family": "Wee", "given": "Shimei", "initials": "S"}, {"family": "Sekyrova", "given": "Petra", "initials": "P"}, {"family": "Schmidt", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Fritz", "given": "Nicolas", "initials": "N"}, {"family": "Dehnisch", "given": "Ivar", "initials": "I"}, {"family": "Kyriatzis", "given": "Gregorios", "initials": "G"}, {"family": "Krafcikova", "given": "Michaela", "initials": "M"}, {"family": "Carson", "given": "Brittany B", "initials": "BB"}, {"family": "Feenstra", "given": "Jennifer M", "initials": "JM"}, {"family": "Marinescu", "given": "Voichita D", "initials": "VD"}, {"family": "Segerman", "given": "Anna", "initials": "A"}, {"family": "Haraldsson", "given": "Martin", "initials": "M"}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "AL", "orcid": "0000-0003-4332-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b014ef7ea0d461b8e2ddb87506b1252.json"}}, {"family": "Hammarstr\u00f6m", "given": "Lars G J", "initials": "LG"}, {"family": "Jenmalm Jensen", "given": "Annika", "initials": "A"}, {"family": "Uhrbom", "given": "Lene", "initials": "L"}, {"family": "Altelaar", "given": "A F Maarten", "initials": "AF"}, {"family": "Linnarsson", "given": "Sten", "initials": "S"}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P"}, {"family": "Trantirek", "given": "Lukas", "initials": "L"}, {"family": "Vincent", "given": "C Theresa", "initials": "CT"}, {"family": "Nelander", "given": "Sven", "initials": "S"}, {"family": "Enger", "given": "Per \u00d8yvind", "initials": "P\u00d8"}, {"family": "And\u00e4ng", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2017-04-01", "journal": {"volume": "77", "issn": "1538-7445", "issue": "7", "pages": "1741-1752", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstream signaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. Our results suggest new therapeutic targets to attack aggressive gliomas. Cancer Res; 77(7); 1741-52. \u00a92017 AACR.", "doi": "10.1158/0008-5472.CAN-16-2274", "pmid": "28087597", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-16-2274"}], "notes": [], "created": "2017-10-20T15:10:26.209Z", "modified": "2025-10-17T13:04:29.305Z"}, {"entity": "publication", "iuid": "e59d31431a4d47d4a41b71c2023ffce6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e59d31431a4d47d4a41b71c2023ffce6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e59d31431a4d47d4a41b71c2023ffce6"}}, "title": "Somatic Ephrin Receptor Mutations Are Associated with Metastasis in Primary Colorectal Cancer.", "authors": [{"family": "Mathot", "given": "Lucy", "initials": "L"}, {"family": "Kundu", "given": "Snehangshu", "initials": "S"}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Svedlund", "given": "Jessica", "initials": "J"}, {"family": "Moens", "given": "Lotte", "initials": "L"}, {"family": "Adlerteg", "given": "Tom", "initials": "T"}, {"family": "Falk-S\u00f6rqvist", "given": "Elin", "initials": "E"}, {"family": "Rendo", "given": "Ver\u00f3nica", "initials": "V"}, {"family": "Bellomo", "given": "Claudia", "initials": "C"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Cortina", "given": "Carme", "initials": "C"}, {"family": "Sundstr\u00f6m", "given": "Magnus", "initials": "M"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A"}, {"family": "Batlle", "given": "Eduard", "initials": "E"}, {"family": "Birgisson", "given": "Helgi", "initials": "H"}, {"family": "Glimelius", "given": "Bengt", "initials": "B"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T"}], "type": "journal article", "published": "2017-04-01", "journal": {"volume": "77", "issn": "1538-7445", "issue": "7", "pages": "1730-1740", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "The contribution of somatic mutations to metastasis of colorectal cancers is currently unknown. To find mutations involved in the colorectal cancer metastatic process, we performed deep mutational analysis of 676 genes in 107 stages II to IV primary colorectal cancer, of which half had metastasized. The mutation prevalence in the ephrin (EPH) family of tyrosine kinase receptors was 10-fold higher in primary tumors of metastatic colorectal than in nonmetastatic cases and preferentially occurred in stage III and IV tumors. Mutational analyses in situ confirmed expression of mutant EPH receptors. To enable functional studies of EPHB1 mutations, we demonstrated that DLD-1 colorectal cancer cells expressing EPHB1 form aggregates upon coculture with ephrin B1 expressing cells. When mutations in the fibronectin type III and kinase domains of EPHB1 were compared with wild-type EPHB1 in DLD-1 colorectal cancer cells, they decreased ephrin B1-induced compartmentalization. These observations provide a mechanistic link between EPHB receptor mutations and metastasis in colorectal cancer. Cancer Res; 77(7); 1730-40. \u00a92017 AACR.", "doi": "10.1158/0008-5472.CAN-16-1921", "pmid": "28108514", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-16-1921"}], "notes": [], "created": "2017-10-31T09:02:56.400Z", "modified": "2021-07-07T13:54:46.167Z"}, {"entity": "publication", "iuid": "ef4cc924f1e54f01bd4c84a213b5e5ec", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ef4cc924f1e54f01bd4c84a213b5e5ec.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ef4cc924f1e54f01bd4c84a213b5e5ec"}}, "title": "Crystal Structure of the Emerging Cancer Target MTHFD2 in Complex with a Substrate-Based Inhibitor.", "authors": [{"family": "Gustafsson", "given": "Robert", "initials": "R"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Gustafsson", "given": "Nina M S", "initials": "NM"}, {"family": "F\u00e4rneg\u00e5rdh", "given": "Katarina", "initials": "K"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Bonagas", "given": "Nadilly", "initials": "N"}, {"family": "Dahllund", "given": "Leif", "initials": "L"}, {"family": "Llona-Minguez", "given": "Sabin", "initials": "S"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Andersson", "given": "Yasmin", "initials": "Y"}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P"}], "type": "journal article", "published": "2017-02-15", "journal": {"volume": "77", "issn": "1538-7445", "issue": "4", "pages": "937-948", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "To sustain their proliferation, cancer cells become dependent on one-carbon metabolism to support purine and thymidylate synthesis. Indeed, one of the most highly upregulated enzymes during neoplastic transformation is MTHFD2, a mitochondrial methylenetetrahydrofolate dehydrogenase and cyclohydrolase involved in one-carbon metabolism. Because MTHFD2 is expressed normally only during embryonic development, it offers a disease-selective therapeutic target for eradicating cancer cells while sparing healthy cells. Here we report the synthesis and preclinical characterization of the first inhibitor of human MTHFD2. We also disclose the first crystal structure of MTHFD2 in complex with a substrate-based inhibitor and the enzyme cofactors NAD+ and inorganic phosphate. Our work provides a rationale for continued development of a structural framework for the generation of potent and selective MTHFD2 inhibitors for cancer treatment. Cancer Res; 77(4); 937-48. \u00a92017 AACR.", "doi": "10.1158/0008-5472.CAN-16-1476", "pmid": "27899380", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-16-1476"}], "notes": "Medicinal Chemistry \u2013 Hit2Lead\r\nProtein Expression and Characterization", "created": "2017-05-08T07:55:19.741Z", "modified": "2025-10-17T13:05:09.030Z"}, {"entity": "publication", "iuid": "6ffde39b841646ddabda81c99083c219", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6ffde39b841646ddabda81c99083c219.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6ffde39b841646ddabda81c99083c219"}}, "title": "Estrogen Receptor \u03b1 Promotes Breast Cancer by Reprogramming Choline Metabolism.", "authors": [{"family": "Jia", "given": "Min", "initials": "M"}, {"family": "Andreassen", "given": "Trygve", "initials": "T"}, {"family": "Jensen", "given": "Lasse", "initials": "L"}, {"family": "Bathen", "given": "Tone Frost", "initials": "TF"}, {"family": "Sinha", "given": "Indranil", "initials": "I"}, {"family": "Gao", "given": "Hui", "initials": "H"}, {"family": "Zhao", "given": "Chunyan", "initials": "C"}, {"family": "Haldosen", "given": "Lars-Arne", "initials": "LA"}, {"family": "Cao", "given": "Yihai", "initials": "Y"}, {"family": "Girnita", "given": "Leonard", "initials": "L"}, {"family": "Moestue", "given": "Siver Andreas", "initials": "SA"}, {"family": "Dahlman-Wright", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2016-10-01", "journal": {"volume": "76", "issn": "1538-7445", "issue": "19", "pages": "5634-5646", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "Estrogen receptor \u03b1 (ER\u03b1) is a key regulator of breast growth and breast cancer development. Here, we report how ER\u03b1 impacts these processes by reprogramming metabolism in malignant breast cells. We employed an integrated approach, combining genome-wide mapping of chromatin-bound ER\u03b1 with estrogen-induced transcript and metabolic profiling, to demonstrate that ER\u03b1 reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline (Cho) metabolism. Cho phosphotransferase CHPT1, identified as a direct ER\u03b1-regulated gene, was required for estrogen-induced effects on Cho metabolism, including increased phosphatidylcholine synthesis. CHPT1 silencing inhibited anchorage-independent growth and cell proliferation, also suppressing early-stage metastasis of tamoxifen-resistant breast cancer cells in a zebrafish xenograft model. Our results showed that ER\u03b1 promotes metabolic alterations in breast cancer cells mediated by its target CHPT1, which this study implicates as a candidate therapeutic target. Cancer Res; 76(19); 5634-46. \u00a92016 AACR.", "doi": "10.1158/0008-5472.CAN-15-2910", "pmid": "27457520", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-15-2910"}], "notes": [], "created": "2017-05-03T12:59:41.181Z", "modified": "2025-10-17T13:03:19.343Z"}, {"entity": "publication", "iuid": "987c9c8129da4379a9ccab3ef61b04fd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/987c9c8129da4379a9ccab3ef61b04fd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/987c9c8129da4379a9ccab3ef61b04fd"}}, "title": "NUDT15 Hydrolyzes 6-Thio-DeoxyGTP to Mediate the Anticancer Efficacy of 6-Thioguanine.", "authors": [{"family": "Valerie", "given": "Nicholas C K", "initials": "NC"}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Page", "given": "Brent D G", "initials": "BD"}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G"}, {"family": "Rehling", "given": "Daniel", "initials": "D"}, {"family": "Carter", "given": "Megan", "initials": "M"}, {"family": "Bevc", "given": "Luka", "initials": "L"}, {"family": "Herr", "given": "Patrick", "initials": "P"}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Sheppard", "given": "Nina G", "initials": "NG"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2016-09-15", "journal": {"volume": "76", "issn": "1538-7445", "issue": "18", "pages": "5501-5511", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "Thiopurines are a standard treatment for childhood leukemia, but like all chemotherapeutics, their use is limited by inherent or acquired resistance in patients. Recently, the nucleoside diphosphate hydrolase NUDT15 has received attention on the basis of its ability to hydrolyze the thiopurine effector metabolites 6-thio-deoxyGTP (6-thio-dGTP) and 6-thio-GTP, thereby limiting the efficacy of thiopurines. In particular, increasing evidence suggests an association between the NUDT15 missense variant, R139C, and thiopurine sensitivity. In this study, we elucidated the role of NUDT15 and NUDT15 R139C in thiopurine metabolism. In vitro and cellular results argued that 6-thio-dGTP and 6-thio-GTP are favored substrates for NUDT15, a finding supported by a crystallographic determination of NUDT15 in complex with 6-thio-GMP. We found that NUDT15 R139C mutation did not affect enzymatic activity but instead negatively influenced protein stability, likely due to a loss of supportive intramolecular bonds that caused rapid proteasomal degradation in cells. Mechanistic investigations in cells indicated that NUDT15 ablation potentiated induction of the DNA damage checkpoint and cancer cell death by 6-thioguanine. Taken together, our results defined how NUDT15 limits thiopurine efficacy and how genetic ablation via the R139C missense mutation confers sensitivity to thiopurine treatment in patients. Cancer Res; 76(18); 5501-11. \u00a92016 AACR.", "doi": "10.1158/0008-5472.CAN-16-0584", "pmid": "27530327", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-16-0584"}, {"db": "pmc", "key": "PMC6847052"}, {"db": "mid", "key": "EMS84823"}], "notes": [], "created": "2017-05-08T07:59:57.345Z", "modified": "2021-07-08T13:01:30.872Z"}, {"entity": "publication", "iuid": "8b928eedd0164decab205054cd5bc0bd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8b928eedd0164decab205054cd5bc0bd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8b928eedd0164decab205054cd5bc0bd"}}, "title": "Metastasis Stimulation by Hypoxia and Acidosis-Induced Extracellular Lipid Uptake Is Mediated by Proteoglycan-Dependent Endocytosis.", "authors": [{"family": "Menard", "given": "Julien A", "initials": "JA"}, {"family": "Christianson", "given": "Helena C", "initials": "HC"}, {"family": "Kucharzewska", "given": "Paulina", "initials": "P"}, {"family": "Bourseau-Guilmain", "given": "Erika", "initials": "E"}, {"family": "Svensson", "given": "Katrin J", "initials": "KJ"}, {"family": "Lindqvist", "given": "Eva", "initials": "E"}, {"family": "Indira Chandran", "given": "Vineesh", "initials": "V"}, {"family": "Kjell\u00e9n", "given": "Lena", "initials": "L"}, {"family": "Welinder", "given": "Charlotte", "initials": "C"}, {"family": "Bengzon", "given": "Johan", "initials": "J"}, {"family": "Johansson", "given": "Maria C", "initials": "MC"}, {"family": "Belting", "given": "Mattias", "initials": "M"}], "type": "journal article", "published": "2016-08-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "76", "issue": "16", "pages": "4828-4840", "issn-l": "0008-5472"}, "abstract": "Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid-storing phenotype and enhanced tumor-forming capacity. Patient glioblastoma tumors and cells under hypoxic and acidic stress acquired a lipid droplet (LD)-loaded phenotype, and showed an increased recruitment of all major lipoproteins, HDL, LDL, and VLDL. Stress-induced LD accumulation was associated with increased spheroid-forming capacity during reoxygenation in vitro and lung metastatic potential in vivo On a mechanistic level, we found no apparent effect of hypoxia on HSPGs, whereas lipoprotein receptors (VLDLR and SR-B1) were transiently upregulated by hypoxia. Importantly, however, using pharmacologic and genetic approaches, we show that stress-mediated lipoprotein uptake is highly dependent on intact HSPG expression. The functional relevance of HSPG in the context of tumor cell stress was evidenced by HSPG-dependent lipoprotein cell signaling activation through the ERK/MAPK pathway and by reversal of the LD-loaded phenotype by targeting of HSPGs. We conclude that HSPGs may have an important role in the adaptive response to major stress factors of the tumor microenvironment, with functional consequences on tumor cell signaling and metastatic potential. Cancer Res; 76(16); 4828-40. \u00a92016 AACR.", "doi": "10.1158/0008-5472.CAN-15-2831", "pmid": "27199348", "labels": {"Structural Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-15-2831"}], "notes": [], "created": "2020-01-27T10:11:08.379Z", "modified": "2021-05-24T15:39:50.288Z"}, {"entity": "publication", "iuid": "84509263ef084dbfa417a9b26a33a0ba", "links": {"self": {"href": "https://publications.scilifelab.se/publication/84509263ef084dbfa417a9b26a33a0ba.json"}, "display": {"href": "https://publications.scilifelab.se/publication/84509263ef084dbfa417a9b26a33a0ba"}}, "title": "Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages.", "authors": [{"family": "Wallerius", "given": "Majken", "initials": "M"}, {"family": "Wallmann", "given": "Tatjana", "initials": "T"}, {"family": "Bartish", "given": "Margarita", "initials": "M"}, {"family": "\u00d6stling", "given": "Jeanette", "initials": "J"}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP"}, {"family": "Nygren", "given": "Emma", "initials": "E"}, {"family": "Pangigadde", "given": "Pradeepa", "initials": "P"}, {"family": "Pellegrini", "given": "Paola", "initials": "P"}, {"family": "Squadrito", "given": "Mario Leonardo", "initials": "ML"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Hartman", "given": "Johan", "initials": "J"}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "De Milito", "given": "Angelo", "initials": "A"}, {"family": "De Palma", "given": "Michele", "initials": "M"}, {"family": "\u00d6stman", "given": "Arne", "initials": "A"}, {"family": "Andersson", "given": "John", "initials": "J"}, {"family": "Rolny", "given": "Charlotte", "initials": "C"}], "type": "journal article", "published": "2016-06-01", "journal": {"volume": "76", "issn": "1538-7445", "issue": "11", "pages": "3166-3178", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "Accumulation of tumor-associated macrophages (TAM) correlates with malignant progression, immune suppression, and poor prognosis. In this study, we defined a critical role for the cell-surface guidance molecule SEMA3A in differential proliferative control of TAMs. Tumor cell-derived SEMA3A restricted the proliferation of protumoral M2 macrophages but increased the proliferation of antitumoral M1, acting through the SEMA3A receptor neuropilin 1. Expansion of M1 macrophages in vivo enhanced the recruitment and activation of natural killer (NK) cells and cytotoxic CD8(+) T cells to tumors, inhibiting their growth. In human breast cancer specimens, we found that immunohistochemical levels of SEMA3A correlated with the expression of genes characteristic of M1 macrophages, CD8(+) T cells, and NK cells, while inversely correlating with established characters of malignancy. In summary, our results illuminate a mechanism whereby the TAM phenotype is controlled and identify the cell-surface molecule SEMA3A as a candidate for therapeutic targeting. Cancer Res; 76(11); 3166-78. \u00a92016 AACR.", "doi": "10.1158/0008-5472.CAN-15-2596", "pmid": "27197153", "labels": {"Tissue Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-15-2596"}], "notes": [], "created": "2017-05-08T07:56:17.500Z", "modified": "2017-11-05T12:48:54.182Z"}, {"entity": "publication", "iuid": "83ba126d87e1479f8b2960d8102e084b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/83ba126d87e1479f8b2960d8102e084b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/83ba126d87e1479f8b2960d8102e084b"}}, "title": "Elevated expression of the C-type lectin CD93 in the glioblastoma vasculature regulates cytoskeletal rearrangements that enhance vessel function and reduce host survival.", "authors": [{"family": "Langenkamp", "given": "Elise", "initials": "E"}, {"family": "Zhang", "given": "Lei", "initials": "L"}, {"family": "Lugano", "given": "Roberta", "initials": "R"}, {"family": "Huang", "given": "Hua", "initials": "H"}, {"family": "Elhassan", "given": "Tamador Elsir Abu", "initials": "TE"}, {"family": "Georganaki", "given": "Maria", "initials": "M"}, {"family": "Bazzar", "given": "Wesam", "initials": "W"}, {"family": "L\u00f6\u00f6f", "given": "Johan", "initials": "J"}, {"family": "Trendelenburg", "given": "George", "initials": "G"}, {"family": "Essand", "given": "Magnus", "initials": "M"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Smits", "given": "Anja", "initials": "A"}, {"family": "Dimberg", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2015-11-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "75", "issue": "21", "pages": "4504-4516", "issn-l": "0008-5472"}, "abstract": "Glioblastoma is an aggressive brain tumor characterized by an abnormal blood vasculature that is hyperpermeable. Here, we report a novel role for CD93 in regulating angiogenesis in this setting by modulating cell-cell and cell-matrix adhesion of endothelial cells. Tissue microarray analysis demonstrated that vascular expression of CD93 was correlated with poor survival in a clinical cohort of patients with high-grade astrocytic glioma. Similarly, intracranial growth in the GL261 mouse model of glioma was delayed significantly in CD93(-/-) hosts, resulting in improved survival compared with wild-type mice. This effect was associated with increased vascular permeability and decreased vascular perfusion of tumors, indicating reduced vessel functionality in the absence of CD93. RNAi-mediated attenuation of CD93 in endothelial cells diminished VEGF-induced tube formation in a three-dimensional collagen gel. CD93 was required for efficient endothelial cell migration and proper cell polarization in vitro. Further, in endothelial cells where CD93 was attenuated, decreased cell spreading led to a severe reduction in cell adhesion, a lack of proper cell contacts, a loss of VE-cadherin, and aberrant actin stress fiber formation. Our results identify CD93 as a key regulator of glioma angiogenesis and vascular function, acting via cytoskeletal rearrangements required for cell-cell and cell-matrix adhesion.", "doi": "10.1158/0008-5472.CAN-14-3636", "pmid": "26363010", "labels": {"Tissue Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-14-3636"}], "notes": [], "created": "2017-11-05T12:54:51.374Z", "modified": "2017-11-05T12:54:51.392Z"}, {"entity": "publication", "iuid": "43c77048d717481c89b773865d802be1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/43c77048d717481c89b773865d802be1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/43c77048d717481c89b773865d802be1"}}, "title": "Genome-wide profiling of AP-1-regulated transcription provides insights into the invasiveness of triple-negative breast cancer.", "authors": [{"family": "Zhao", "given": "Chunyan", "initials": "C"}, {"family": "Qiao", "given": "Yichun", "initials": "Y"}, {"family": "Jonsson", "given": "Philip", "initials": "P"}, {"family": "Wang", "given": "Jian", "initials": "J"}, {"family": "Xu", "given": "Li", "initials": "L"}, {"family": "Rouhi", "given": "Pegah", "initials": "P"}, {"family": "Sinha", "given": "Indranil", "initials": "I"}, {"family": "Cao", "given": "Yihai", "initials": "Y"}, {"family": "Williams", "given": "Cecilia", "initials": "C"}, {"family": "Dahlman-Wright", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2014-07-15", "journal": {"volume": "74", "issn": "1538-7445", "issue": "14", "pages": "3983-3994", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell-cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties.", "doi": "10.1158/0008-5472.CAN-13-3396", "pmid": "24830720", "labels": {"Bioinformatics and Expression Analysis (BEA)": null}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-13-3396"}], "notes": [], "created": "2017-05-04T15:03:17.831Z", "modified": "2017-05-30T12:42:03.827Z"}, {"entity": "publication", "iuid": "02e1f5c00470444babe5e686e12f9819", "links": {"self": {"href": "https://publications.scilifelab.se/publication/02e1f5c00470444babe5e686e12f9819.json"}, "display": {"href": "https://publications.scilifelab.se/publication/02e1f5c00470444babe5e686e12f9819"}}, "title": "STC1 expression by cancer-associated fibroblasts drives metastasis of colorectal cancer.", "authors": [{"family": "Pe\u00f1a", "given": "Cristina", "initials": "C"}, {"family": "C\u00e9spedes", "given": "Mar\u00eda Virtudes", "initials": "MV"}, {"family": "Lindh", "given": "Maja Bradic", "initials": "MB"}, {"family": "Kiflemariam", "given": "Sara", "initials": "S"}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Edqvist", "given": "Per-Henrik", "initials": "PH"}, {"family": "H\u00e4ggl\u00f6f", "given": "Christina", "initials": "C"}, {"family": "Birgisson", "given": "Helgi", "initials": "H"}, {"family": "Bojmar", "given": "Linda", "initials": "L"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Sandstr\u00f6m", "given": "Per", "initials": "P"}, {"family": "Olsson", "given": "Eleonor", "initials": "E"}, {"family": "Veerla", "given": "Srinivas", "initials": "S"}, {"family": "Gallardo", "given": "Alberto", "initials": "A"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T"}, {"family": "Chang", "given": "Andy C-M", "initials": "AC"}, {"family": "Reddel", "given": "Roger R", "initials": "RR"}, {"family": "Mangues", "given": "Ram\u00f3n", "initials": "R"}, {"family": "Augsten", "given": "Martin", "initials": "M"}, {"family": "Ostman", "given": "Arne", "initials": "A"}], "type": "journal article", "published": "2013-02-15", "journal": {"volume": "73", "issn": "1538-7445", "issue": "4", "pages": "1287-1297", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis.", "doi": "10.1158/0008-5472.CAN-12-1875", "pmid": "23243022", "labels": {"Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-12-1875"}], "notes": [], "created": "2017-05-04T14:55:55.926Z", "modified": "2017-05-30T12:51:06.500Z"}, {"entity": "publication", "iuid": "a06837e4b02a4214a16a4251b1951a98", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a06837e4b02a4214a16a4251b1951a98.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a06837e4b02a4214a16a4251b1951a98"}}, "title": "Genome-wide mapping of estrogen receptor-beta-binding regions reveals extensive cross-talk with transcription factor activator protein-1.", "authors": [{"family": "Zhao", "given": "Chunyan", "initials": "C"}, {"family": "Gao", "given": "Hui", "initials": "H"}, {"family": "Liu", "given": "Yawen", "initials": "Y"}, {"family": "Papoutsi", "given": "Zoi", "initials": "Z"}, {"family": "Jaffrey", "given": "Sadaf", "initials": "S"}, {"family": "Gustafsson", "given": "Jan-Ake", "initials": "JA"}, {"family": "Dahlman-Wright", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2010-06-15", "journal": {"volume": "70", "issn": "1538-7445", "issue": "12", "pages": "5174-5183", "title": "Cancer Res.", "issn-l": "0008-5472"}, "abstract": "Estrogen signaling can occur through a nonclassical pathway involving the interaction of estrogen receptors (ER) with other transcription factors such as activator protein-1 (AP-1) and SP-1. However, there is little mechanistic understanding about this pathway, with conflicting results from in vitro investigations. In this study, we applied the ChIP-on-chip approach to identify ERbeta-binding sites on a genome-wide scale, identifying 1,457 high-confidence binding sites in ERbeta-overexpressing MCF7 breast cancer cells. Genes containing ERbeta-binding sites can be regulated by E2. Notably, approximately 60% of the genomic regions bound by ERbeta contained AP-1-like binding regions and estrogen response element-like sites, suggesting a functional association between AP-1 and ERbeta signaling. Chromatin immunoprecipitation (ChIP) analysis confirmed the association of AP-1, which is composed of the oncogenic transcription factors c-Fos and c-Jun, to ERbeta-bound DNA regions. Using a re-ChIP assay, we showed co-occupancy of ERbeta and AP-1 on chromatin. Short interfering RNA-mediated knockdown of c-Fos or c-Jun expression decreased ERbeta recruitment to chromatin, consistent with the role of AP-1 in mediating estrogen signaling in breast cancer cells. Additionally, ERalpha and ERbeta recruitment to AP-1/ERbeta target regions exhibited gene-dependent differences in response to antiestrogens. Together, our results broaden insights into ERbeta DNA-binding at the genomic level by revealing crosstalk with the AP-1 transcription factor.", "doi": "10.1158/0008-5472.CAN-09-4407", "pmid": "20501845", "labels": {"Bioinformatics and Expression Analysis (BEA)": null}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-09-4407"}], "notes": [], "created": "2017-05-04T15:03:04.225Z", "modified": "2017-05-30T12:38:41.916Z"}], "created": "2017-05-09T09:12:38.913Z", "modified": "2020-11-27T13:14:04.995Z"}