{"entity": "journal", "iuid": "65f8bcdff72c4d59890e0bb178b23b53", "timestamp": "2026-07-11T15:14:42.523Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Oncogene.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Oncogene"}}, "title": "Oncogene", "issn": "1476-5594", "issn-l": "0950-9232", "publications_count": 10, "publications": [{"entity": "publication", "iuid": "4a95cb368b7e43af872e0dd1190cd040", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4a95cb368b7e43af872e0dd1190cd040.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4a95cb368b7e43af872e0dd1190cd040"}}, "title": "The T\u03b2RI promotes migration and metastasis through thrombospondin 1 and ITGAV in prostate cancer cells.", "authors": [{"family": "Mu", "given": "Yabing", "initials": "Y", "orcid": "0000-0003-3193-1425", "researcher": {"href": "https://publications.scilifelab.se/researcher/626d44f4c6d7498ea7e2690e9f7008d5.json"}}, {"family": "Wallenius", "given": "Anders", "initials": "A"}, {"family": "Zang", "given": "Guangxiang", "initials": "G"}, {"family": "Zhu", "given": "Shaochun", "initials": "S", "orcid": "0000-0001-9945-6718", "researcher": {"href": "https://publications.scilifelab.se/researcher/50c472868ea0437bb9a5a1b0a574bc39.json"}}, {"family": "Rudolfsson", "given": "Stina", "initials": "S"}, {"family": "Aripaka", "given": "Karthik", "initials": "K", "orcid": "0000-0001-5071-6187", "researcher": {"href": "https://publications.scilifelab.se/researcher/2622fdbe964f4f99810cdc20c67a9fe0.json"}}, {"family": "Bergh", "given": "Anders", "initials": "A", "orcid": "0000-0001-5163-5821", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba7945f3e27f4628ba29c7003b3bdf36.json"}}, {"family": "Mateus", "given": "Andr\u00e9", "initials": "A"}, {"family": "Landstr\u00f6m", "given": "Mar\u00e9ne", "initials": "M", "orcid": "0000-0001-6737-7230", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2f02fcfb1c1497d81a6f343bc0e6928.json"}}], "type": "journal article", "published": "2024-11-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "issn-l": "0950-9232", "volume": "43", "issue": "45", "pages": "3321-3334"}, "abstract": "TGF\u03b2 potently modifies the extracellular matrix (ECM), which is thought to favor tumor cell invasion. However, the mechanism whereby the cancer cells employ the ECM proteins to facilitate their motility is largely unknown. In this study we used RNA-seq and proteomic analysis to examine the proteins secreted by castration-resistant prostate cancer (CRPC) cells upon TGF\u03b2 treatment and found that thrombospondin 1 (THBS1) was observed to be one of the predominant proteins. The CRISPR Cas9, or siRNA techniques was used to downregulate TGF\u03b2 type I receptor (T\u03b2RI) to interfere with TGF\u03b2 signaling in various cancer cells in vitro. The interaction of ECM proteins with the T\u03b2RI in the migratory prostate cancer cells in response to TGF\u03b21 was demonstrated by several different techniques to reveal that THBS1 mediates cell migration by interacting with integrin subunit alpha V (ITGAV) and T\u03b2RI. Deletion of T\u03b2RI or THBS1 in cancer cells prevented their migration and invasion. THBS1 belongs to a group of tumorigenic ECM proteins induced via TGF\u03b2 signaling in CRPC cells, and high expression of THBS1 in human prostate cancer tissues correlated with the degree of malignancy. TGF\u03b2-induced production of THBS1 through T\u03b2RI facilitates the invasion and metastasis of CRPC cells as shown in vivo xenograft animal experiments.", "doi": "10.1038/s41388-024-03165-3", "pmid": "39304722", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41388-024-03165-3"}], "notes": [], "created": "2024-11-05T07:21:43.281Z", "modified": "2024-11-15T09:56:41.242Z"}, {"entity": "publication", "iuid": "64e68ef4034c420a969d2379ad26bb17", "links": {"self": {"href": "https://publications.scilifelab.se/publication/64e68ef4034c420a969d2379ad26bb17.json"}, "display": {"href": "https://publications.scilifelab.se/publication/64e68ef4034c420a969d2379ad26bb17"}}, "title": "Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence.", "authors": [{"family": "Reid", "given": "Steven E", "initials": "SE"}, {"family": "Pantaleo", "given": "Jessica", "initials": "J"}, {"family": "Bolivar", "given": "Paulina", "initials": "P"}, {"family": "Bocci", "given": "Matteo", "initials": "M", "orcid": "0000-0002-8774-0006", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff52ba58701141f88766777a3d7ef21e.json"}}, {"family": "Sj\u00f6lund", "given": "Jonas", "initials": "J", "orcid": "0000-0002-6992-3415", "researcher": {"href": "https://publications.scilifelab.se/researcher/eccac6b320244409879d5bac740f5202.json"}}, {"family": "Morsing", "given": "Mikkel", "initials": "M", "orcid": "0000-0001-8322-8796", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc8997c361484b0092e585a696c727e0.json"}}, {"family": "Cordero", "given": "Eugenia", "initials": "E"}, {"family": "Larsson", "given": "Sara", "initials": "S", "orcid": "0000-0002-0002-0779", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa131bd3ad94e8684b4d89a098b3482.json"}}, {"family": "Malmberg", "given": "Maria", "initials": "M"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B"}, {"family": "Pietras", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6738-4705", "researcher": {"href": "https://publications.scilifelab.se/researcher/5be0a3ec07654822a91df964eab1d6e4.json"}}], "type": "journal article", "published": "2024-04-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "43", "issue": "15", "pages": "1113-1126", "issn-l": "0950-9232"}, "abstract": "Advanced breast cancers represent a major therapeutic challenge due to their refractoriness to treatment. Cancer-associated fibroblasts (CAFs) are the most abundant constituents of the tumor microenvironment and have been linked to most hallmarks of cancer. However, the influence of CAFs on therapeutic outcome remains largely unchartered. Here, we reveal that spatial coincidence of abundant CAF infiltration with malignant cells was associated with reduced estrogen receptor (ER)-\u03b1 expression and activity in luminal breast tumors. Notably, CAFs mediated estrogen-independent tumor growth by selectively regulating ER-\u03b1 signaling. Whereas most prototypical estrogen-responsive genes were suppressed, CAFs maintained gene expression related to therapeutic resistance, basal-like differentiation, and invasion. A functional drug screen in co-cultures identified effector pathways involved in the CAF-induced regulation of ER-\u03b1 signaling. Among these, the Transforming Growth Factor-\u03b2 and the Janus kinase signaling cascades were validated as actionable targets to counteract the CAF-induced modulation of ER-\u03b1 activity. Finally, genes that were downregulated in cancer cells by CAFs were predictive of poor response to endocrine treatment. In conclusion, our work reveals that CAFs directly control the luminal breast cancer phenotype by selectively modulating ER-\u03b1 expression and transcriptional function, and further proposes novel targets to disrupt the crosstalk between CAFs and tumor cells to reinstate treatment response to endocrine therapy in patients.", "doi": "10.1038/s41388-024-02973-x", "pmid": "38388711", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10997519"}, {"db": "pii", "key": "10.1038/s41388-024-02973-x"}], "notes": [], "created": "2024-04-11T12:06:19.191Z", "modified": "2025-10-17T13:04:27.393Z"}, {"entity": "publication", "iuid": "028827c58bea4f14bbedb8ef627db6fc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/028827c58bea4f14bbedb8ef627db6fc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/028827c58bea4f14bbedb8ef627db6fc"}}, "title": "SFRP2 induces a mesenchymal subtype transition by suppression of SOX2 in glioblastoma.", "authors": [{"family": "Guo", "given": "Min", "initials": "M", "orcid": "0000-0002-2291-1230", "researcher": {"href": "https://publications.scilifelab.se/researcher/b31e97bd7c2b4cb49b173189d515c2dc.json"}}, {"family": "Goudarzi", "given": "Kaveh M", "initials": "KM"}, {"family": "Abedi", "given": "Shiva", "initials": "S"}, {"family": "Pieber", "given": "Melanie", "initials": "M"}, {"family": "Sj\u00f6berg", "given": "Elin", "initials": "E", "orcid": "0000-0002-8799-4874", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd51131ccec248aea0bcf013a7da3296.json"}}, {"family": "Behnan", "given": "Jinan", "initials": "J", "orcid": "0000-0001-5780-0971", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fbacfae35ad4364b5058e432aa6e6df.json"}}, {"family": "Zhang", "given": "Xing-Mei", "initials": "XM"}, {"family": "Harris", "given": "Robert A", "initials": "RA"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Nist\u00e9r", "given": "Monica", "initials": "M", "orcid": "0000-0002-1261-3790", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1dc80e61f574293a190f2f3ef464988.json"}}, {"family": "H\u00e4gerstrand", "given": "Daniel", "initials": "D", "orcid": "0000-0001-7270-0776", "researcher": {"href": "https://publications.scilifelab.se/researcher/35a683cea1874ac290d91c325a648be8.json"}}], "type": "journal article", "published": "2021-08-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "40", "issue": "32", "pages": "5066-5080", "issn-l": "0950-9232"}, "abstract": "Intratumoral heterogeneity is a characteristic of glioblastomas that contain an intermixture of cell populations displaying different glioblastoma subtype gene expression signatures. Proportions of these populations change during tumor evolution, but the occurrence and regulation of glioblastoma subtype transition is not well described. To identify regulators of glioblastoma subtypes we utilized a combination of in vitro experiments and in silico analyses, using experimentally generated as well as publicly available data. Through this combined approach SOX2 was identified to confer a proneural glioblastoma subtype gene expression signature. SFRP2 was subsequently identified as a SOX2-antagonist, able to induce a mesenchymal glioblastoma subtype signature. A subset of patient glioblastoma samples with high SFRP2 and low SOX2 expression was particularly enriched with mesenchymal subtype samples. Phenotypically, SFRP2 decreased tumor sphere formation, stemness as assessed by limiting dilution assay, and overall cell proliferation but increased cell motility, whereas SOX2 induced the opposite effects. Furthermore, an SFRP2/non-canonical-WNT/KLF4/PDGFR/phospho-AKT/SOX2 signaling axis was found to be involved in the mesenchymal transition. Analysis of human tumor tissue spatial gene expression patterns showed distinct expression of SFRP2- and SOX2-correlated genes in vascular and cellular areas, respectively. Finally, conditioned media from SFRP2 overexpressing cells increased CD206 on macrophages. Together, these findings present SFRP2 as a SOX2-antagonist with the capacity to induce a mesenchymal subtype transition in glioma cells located in vascular tumor areas, highlighting its role in glioblastoma tumor evolution and intratumoral heterogeneity.", "doi": "10.1038/s41388-021-01825-2", "pmid": "34021259", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41388-021-01825-2"}, {"db": "pmc", "key": "PMC8363098"}], "notes": [], "created": "2021-10-01T09:01:02.317Z", "modified": "2022-03-29T11:45:30.466Z"}, {"entity": "publication", "iuid": "f2d9ecae73c44d238c01ab6c6878d296", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f2d9ecae73c44d238c01ab6c6878d296.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f2d9ecae73c44d238c01ab6c6878d296"}}, "title": "LY6K-AS lncRNA is a lung adenocarcinoma prognostic biomarker and regulator of mitotic progression.", "authors": [{"family": "Ali", "given": "Mohamad Moustafa", "initials": "MM"}, {"family": "Di Marco", "given": "Mirco", "initials": "M", "orcid": "0000-0001-8890-233X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406c87db9604c1e863736eb7bd11bf1.json"}}, {"family": "Mahale", "given": "Sagar", "initials": "S"}, {"family": "Jachimowicz", "given": "Daniel", "initials": "D"}, {"family": "Kosalai", "given": "Subazini Thankaswamy", "initials": "ST"}, {"family": "Reischl", "given": "Silke", "initials": "S", "orcid": "0000-0003-4822-4137", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf139e277ad14d7caf0bfe88ef9f34d2.json"}}, {"family": "Statello", "given": "Luisa", "initials": "L"}, {"family": "Mishra", "given": "Kankadeb", "initials": "K"}, {"family": "Darnfors", "given": "Catarina", "initials": "C"}, {"family": "Kanduri", "given": "Meena", "initials": "M"}, {"family": "Kanduri", "given": "Chandrasekhar", "initials": "C", "orcid": "0000-0001-6271-9078", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8da9c5c5d0c48f9ae08549027375512.json"}}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "40", "issue": "13", "pages": "2463-2478", "issn-l": "0950-9232"}, "abstract": "Recent advances in genomics unraveled several actionable mutational drivers in lung cancer, leading to promising therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors. However, the tumors' acquired resistance to the newly-developed as well as existing therapies restricts life quality improvements. Therefore, we investigated the noncoding portion of the human transcriptome in search of alternative actionable targets. We identified an antisense transcript, LY6K-AS, with elevated expression in lung adenocarcinoma (LUAD) patients, and its higher expression in LUAD patients predicts poor survival outcomes. LY6K-AS abrogation interfered with the mitotic progression of lung cancer cells resulting in unfaithful chromosomal segregation. LY6K-AS interacts with and stabilizes 14-3-3 proteins to regulate the transcription of kinetochore and mitotic checkpoint proteins. We also show that LY6K-AS regulates the levels of histone H3 lysine 4 trimethylation (H3K4me3) at the promoters of kinetochore members. Cisplatin treatment and LY6K-AS silencing affect many common pathways enriched in cell cycle-related functions. LY6K-AS silencing affects the growth of xenografts derived from wildtype and cisplatin-resistant lung cancer cells. Collectively, these data indicate that LY6K-AS silencing is a promising therapeutic option for LUAD that inhibits oncogenic mitotic progression.", "doi": "10.1038/s41388-021-01696-7", "pmid": "33674747", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41388-021-01696-7"}], "notes": [], "created": "2023-02-16T08:13:43.139Z", "modified": "2023-02-16T08:13:43.241Z"}, {"entity": "publication", "iuid": "420d57a9a28043029a871feaf5d57b7f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/420d57a9a28043029a871feaf5d57b7f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/420d57a9a28043029a871feaf5d57b7f"}}, "title": "PKC\u03b6 facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model", "authors": [{"family": "Zang", "given": "Guangxiang", "initials": "G"}, {"family": "Mu", "given": "Yabing", "initials": "Y"}, {"family": "Gao", "given": "Linlin", "initials": "L"}, {"family": "Bergh", "given": "Anders", "initials": "A"}, {"family": "Landstr\u00f6m", "given": "Marene", "initials": "M"}], "type": "journal-article", "published": "2019-05-00", "journal": {"volume": "38", "issn": "1476-5594", "issue": "22", "pages": "4215-4231", "title": "Oncogene", "issn-l": "0950-9232"}, "abstract": "Prostate cancer disseminates primarily into the adjacent lymph nodes, which is related to a poor outcome. Atypical protein kinase C \u03b6 (PKC\u03b6) is highly expressed in aggressive prostate cancer and correlates with Gleason score, clinical stage, and poor prognosis. Here, we report the molecular mechanisms of PKC\u03b6 in lymphatic metastasis during prostate cancer progression. Using zinc-finger nuclease technology or PKC\u03b6 shRNA lentiviral particles, and orthotopic mouse xenografts, we show that PKC\u03b6-knockout or knockdown from aggressive prostate cancer (PC3 and PC3U) cells, decreasesd tumor growth and lymphatic metastasis in vivo. Intriguingly, PKC\u03b6-knockout or knockdown impaired the activation of AKT, ERK, and NF-\u03baB signaling in prostate cancer cells, thereby impairing the expression of lymphangiogenic factors and macrophage recruitment, resulting in aberrant lymphangiogenesis. Moreover, PKC\u03b6 regulated the expression of hyaluronan synthase enzymes, which is important for hyaluronan-mediated lymphatic drainage and tumor dissemination. Thus, PKC\u03b6 plays a crucial oncogenic role in the lymphatic metastasis of prostate cancer and is predicted to be a novel therapeutic target for prostate cancer.", "doi": "10.1038/s41388-019-0722-9", "pmid": "30705401", "labels": {"National Genomics Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [], "notes": [], "created": "2019-11-25T15:08:43.727Z", "modified": "2020-01-21T13:56:17.596Z"}, {"entity": "publication", "iuid": "f061f70eb9734def938dd0213c971296", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f061f70eb9734def938dd0213c971296.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f061f70eb9734def938dd0213c971296"}}, "title": "Notch signaling promotes a HIF2\u03b1-driven hypoxic response in multiple tumor cell types.", "authors": [{"family": "Mutvei", "given": "Anders P", "initials": "AP"}, {"family": "Landor", "given": "Sebastian K-J", "initials": "SK"}, {"family": "Fox", "given": "Rhys", "initials": "R"}, {"family": "Braune", "given": "Eike-Benjamin", "initials": "EB"}, {"family": "Tsoi", "given": "Yat Long", "initials": "YL"}, {"family": "Phoon", "given": "Yee Peng", "initials": "YP"}, {"family": "Sahlgren", "given": "Cecilia", "initials": "C"}, {"family": "Hartman", "given": "Johan", "initials": "J", "orcid": "0000-0002-6500-8527", "researcher": {"href": "https://publications.scilifelab.se/researcher/da7cefda6e00463d8ba95fc63eeb8f0a.json"}}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "Jin", "given": "Shaobo", "initials": "S"}, {"family": "Lendahl", "given": "Urban", "initials": "U"}], "type": "journal article", "published": "2018-11-00", "journal": {"volume": "37", "issn": "1476-5594", "issue": "46", "title": "Oncogene", "pages": "6083-6095", "issn-l": "0950-9232"}, "abstract": "Hyperactivation of Notch signaling and the cellular hypoxic response are frequently observed in cancers, with increasing reports of connections to tumor initiation and progression. The two signaling mechanisms are known to intersect, but while it is well established that hypoxia regulates Notch signaling, less is known about whether Notch can regulate the cellular hypoxic response. We now report that Notch signaling specifically controls expression of HIF2\u03b1, a key mediator of the cellular hypoxic response. Transcriptional upregulation of HIF2\u03b1 by Notch under normoxic conditions leads to elevated HIF2\u03b1 protein levels in primary breast cancer cells as well as in human breast cancer, medulloblastoma, and renal cell carcinoma cell lines. The elevated level of HIF2\u03b1 protein was in certain tumor cell types accompanied by downregulation of HIF1\u03b1 protein levels, indicating that high Notch signaling may drive a HIF1\u03b1-to-HIF2\u03b1 switch. At the transcriptome level, the presence of HIF2\u03b1 was required for approximately 21% of all Notch-induced genes: among the 1062 genes that were upregulated by Notch in medulloblastoma cells during normoxia, upregulation was abrogated in 227 genes when HIF2\u03b1 expression was knocked down by HIF2\u03b1 siRNA. In conclusion, our data show that Notch signaling affects the hypoxic response via regulation of HIF2\u03b1, which may be important for future cancer therapies.", "doi": "10.1038/s41388-018-0400-3", "pmid": "29993038", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6237764"}, {"db": "pii", "key": "10.1038/s41388-018-0400-3"}], "notes": [], "created": "2018-10-31T19:48:30.853Z", "modified": "2024-01-16T13:48:45.231Z"}, {"entity": "publication", "iuid": "4d8cc303c0d544f3b22c70a8591dffd8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4d8cc303c0d544f3b22c70a8591dffd8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4d8cc303c0d544f3b22c70a8591dffd8"}}, "title": "Combined BET bromodomain and CDK2 inhibition in MYC-driven medulloblastoma.", "authors": [{"family": "Bolin", "given": "Sara", "initials": "S"}, {"family": "Borgenvik", "given": "Anna", "initials": "A"}, {"family": "Persson", "given": "Camilla U", "initials": "CU"}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A"}, {"family": "Qi", "given": "Jun", "initials": "J"}, {"family": "Bradner", "given": "James E", "initials": "JE"}, {"family": "Weiss", "given": "William A", "initials": "WA"}, {"family": "Cho", "given": "Yoon-Jae", "initials": "YJ"}, {"family": "Weishaupt", "given": "Holger", "initials": "H"}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ"}], "type": "journal article", "published": "2018-05-00", "journal": {"volume": "37", "issn": "1476-5594", "issue": "21", "pages": "2850-2862", "title": "Oncogene", "issn-l": "0950-9232"}, "abstract": "Medulloblastoma (MB) is the most common malignant brain tumor in children. MYC genes are frequently amplified and correlate with poor prognosis in MB. BET bromodomains recognize acetylated lysine residues and often promote and maintain MYC transcription. Certain cyclin-dependent kinases (CDKs) are further known to support MYC stabilization in tumor cells. In this report, MB cells were suppressed by combined targeting of MYC expression and MYC stabilization using BET bromodomain inhibition and CDK2 inhibition, respectively. Such combination treatment worked synergistically and caused cell cycle arrest as well as massive apoptosis. Immediate transcriptional changes from this combined MYC blockade were found using RNA-Seq profiling and showed remarkable similarities to changes in MYC target gene expression when MYCN was turned off with doxycycline in our MYCN-inducible animal model for Group 3 MB. In addition, the combination treatment significantly prolonged survival as compared to single-agent therapy in orthotopically transplanted human Group 3 MB with MYC amplifications. Our data suggest that dual inhibition of CDK2 and BET bromodomains can be a novel treatment approach for suppressing MYC-driven cancer.", "doi": "10.1038/s41388-018-0135-1", "pmid": "29511348", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41388-018-0135-1"}, {"db": "pmc", "key": "PMC5966365"}], "notes": [], "created": "2018-10-15T09:57:41.272Z", "modified": "2024-01-16T13:48:46.443Z"}, {"entity": "publication", "iuid": "1ca13a5dbc2c44329bbbefec4d917ee0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1ca13a5dbc2c44329bbbefec4d917ee0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1ca13a5dbc2c44329bbbefec4d917ee0"}}, "title": "microRNAs with AAGUGC seed motif constitute an integral part of an oncogenic signaling network.", "authors": [{"family": "Zhou", "given": "Y", "initials": "Y"}, {"family": "Frings", "given": "O", "initials": "O"}, {"family": "Branca", "given": "R M", "initials": "RM"}, {"family": "Boekel", "given": "J", "initials": "J"}, {"family": "le Sage", "given": "C", "initials": "C"}, {"family": "Fredlund", "given": "E", "initials": "E"}, {"family": "Agami", "given": "R", "initials": "R"}, {"family": "Orre", "given": "L M", "initials": "LM"}], "type": "journal article", "published": "2017-02-09", "journal": {"volume": "36", "issn": "1476-5594", "issue": "6", "pages": "731-745", "title": "Oncogene", "issn-l": "0950-9232"}, "abstract": "microRNA (miRNA) dysregulation is a common feature of cancer cells, but the complex roles of miRNAs in cancer are not fully elucidated. Here, we used functional genomics to identify oncogenic miRNAs in non-small cell lung cancer and evaluate their impact on response to epidermal growth factor (EGFR)-targeting therapy. Our data demonstrate that miRNAs with an AAGUGC motif in their seed sequence increase both cancer cell proliferation and sensitivity to EGFR inhibitors. Global transcriptomics, proteomics and target prediction resulted in the identification of several tumor suppressors involved in the G1/S transition as AAGUGC-miRNA targets. The clinical implications of our findings were evaluated by analysis of AAGUGC-miRNA expression in multiple cancer types, supporting the link between this miRNA seed family, their tumor suppressor targets and cancer cell proliferation. In conclusion, we propose the AAGUGC seed motif as an oncomotif and that oncomotif-miRNAs promote cancer cell proliferation. These findings have potential therapeutic implications, especially in selecting patients for EGFR-targeting therapy.", "doi": "10.1038/onc.2016.242", "pmid": "27477696", "labels": {"National Genomics Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support and Infrastructure": "Collaborative", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "onc2016242"}, {"db": "pmc", "key": "PMC5311252"}], "notes": [], "created": "2017-05-03T13:00:40.536Z", "modified": "2020-01-21T13:56:16.909Z"}, {"entity": "publication", "iuid": "119244bc942c4e0da3c251f66062cc10", "links": {"self": {"href": "https://publications.scilifelab.se/publication/119244bc942c4e0da3c251f66062cc10.json"}, "display": {"href": "https://publications.scilifelab.se/publication/119244bc942c4e0da3c251f66062cc10"}}, "title": "Aberrant activation of the PI3K/mTOR pathway promotes resistance to sorafenib in AML.", "authors": [{"family": "Lindblad", "given": "O", "initials": "O"}, {"family": "Cordero", "given": "E", "initials": "E"}, {"family": "Puissant", "given": "A", "initials": "A"}, {"family": "Macaulay", "given": "L", "initials": "L"}, {"family": "Ramos", "given": "A", "initials": "A"}, {"family": "Kabir", "given": "N N", "initials": "NN"}, {"family": "Sun", "given": "J", "initials": "J"}, {"family": "Vallon-Christersson", "given": "J", "initials": "J"}, {"family": "Haraldsson", "given": "K", "initials": "K"}, {"family": "Hemann", "given": "M T", "initials": "MT"}, {"family": "Borg", "given": "\u00c5", "initials": "\u00c5"}, {"family": "Levander", "given": "F", "initials": "F"}, {"family": "Stegmaier", "given": "K", "initials": "K"}, {"family": "Pietras", "given": "K", "initials": "K"}, {"family": "R\u00f6nnstrand", "given": "L", "initials": "L"}, {"family": "Kazi", "given": "J U", "initials": "JU"}], "type": "journal article", "published": "2016-09-29", "journal": {"volume": "35", "issn": "1476-5594", "issue": "39", "pages": "5119-5131", "title": "Oncogene", "issn-l": "0950-9232"}, "abstract": "Therapy directed against oncogenic FLT3 has been shown to induce response in patients with acute myeloid leukemia (AML), but these responses are almost always transient. To address the mechanism of FLT3 inhibitor resistance, we generated two resistant AML cell lines by sustained treatment with the FLT3 inhibitor sorafenib. Parental cell lines carry the FLT3-ITD (tandem duplication) mutation and are highly responsive to FLT3 inhibitors, whereas resistant cell lines display resistance to multiple FLT3 inhibitors. Sanger sequencing and protein mass-spectrometry did not identify any acquired mutations in FLT3 in the resistant cells. Moreover, sorafenib treatment effectively blocked FLT3 activation in resistant cells, whereas it was unable to block colony formation or cell survival, suggesting that the resistant cells are no longer FLT3 dependent. Gene expression analysis of sensitive and resistant cell lines, as well as of blasts from patients with sorafenib-resistant AML, suggested an enrichment of the PI3K/mTOR pathway in the resistant phenotype, which was further supported by next-generation sequencing and phospho-specific-antibody array analysis. Furthermore, a selective PI3K/mTOR inhibitor, gedatolisib, efficiently blocked proliferation, colony and tumor formation, and induced apoptosis in resistant cell lines. Gedatolisib significantly extended survival of mice in a sorafenib-resistant AML patient-derived xenograft model. Taken together, our data suggest that aberrant activation of the PI3K/mTOR pathway in FLT3-ITD-dependent AML results in resistance to drugs targeting FLT3.", "doi": "10.1038/onc.2016.41", "pmid": "26999641", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "onc201641"}], "notes": [], "created": "2017-05-03T13:00:40.848Z", "modified": "2020-01-21T13:53:21.224Z"}, {"entity": "publication", "iuid": "f8d98b5701f9453384e18ca97f67e393", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f8d98b5701f9453384e18ca97f67e393.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f8d98b5701f9453384e18ca97f67e393"}}, "title": "Oncoprotein stabilization in brain tumors.", "authors": [{"family": "Hede", "given": "S-M", "initials": "SM"}, {"family": "Savov", "given": "V", "initials": "V"}, {"family": "Weishaupt", "given": "H", "initials": "H"}, {"family": "Sangfelt", "given": "O", "initials": "O"}, {"family": "Swartling", "given": "F J", "initials": "FJ"}], "type": "journal article", "published": "2014-09-25", "journal": {"volume": "33", "issn": "1476-5594", "issue": "39", "pages": "4709-4721", "title": "Oncogene", "issn-l": "0950-9232"}, "abstract": "Proteins involved in promoting cell proliferation and viability need to be timely expressed and carefully controlled for the proper development of the brain but also efficiently degraded in order to prevent cells from becoming brain cancer cells. A major pathway for targeted protein degradation in cells is the ubiquitin-proteasome system (UPS). Oncoproteins that drive tumor development and tumor maintenance are often deregulated and stabilized in malignant cells. This can occur when oncoproteins escape degradation by the UPS because of mutations in either the oncoprotein itself or in the UPS components responsible for recognition and ubiquitylation of the oncoprotein. As the pathogenic accumulation of an oncoprotein can lead to effectively sustained cell growth, viability and tumor progression, it is an indisputable target for cancer treatment. The most common types of malignant brain tumors in children and adults are medulloblastoma and glioma, respectively. Here, we review different ways of how deregulated proteolysis of oncoproteins involved in major signaling cancer pathways contributes to medulloblastoma and glioma development. We also describe means of targeting relevant oncoproteins in brain tumors with treatments affecting their stability or therapeutic strategies directed against the UPS itself.", "doi": "10.1038/onc.2013.445", "pmid": "24166497", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "onc2013445"}], "notes": [], "created": "2017-05-04T14:58:50.357Z", "modified": "2020-01-21T13:56:06.423Z"}], "created": "2017-05-09T09:12:52.093Z", "modified": "2020-11-27T13:14:04.025Z"}