{"entity": "researcher", "timestamp": "2026-08-16T10:45:42.555Z", "family": "Mu", "given": "Yabing", "initials": "Y", "orcid": "0000-0003-3193-1425", "affiliations": ["Department of Medical Bioscience, Ume\u00e5 University, Ume\u00e5, Sweden. yabing.mu@umu.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/626d44f4c6d7498ea7e2690e9f7008d5.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/626d44f4c6d7498ea7e2690e9f7008d5"}}, "publications": [{"entity": "publication", "iuid": "d831391ebc12404d9d3e99a061f12e86", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d831391ebc12404d9d3e99a061f12e86.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d831391ebc12404d9d3e99a061f12e86"}}, "title": "Targeting oncogenic T\u03b2RI signaling inhibits androgen-independent prostate cancer growth and metastasis.", "authors": [{"family": "Flodbring Larsson", "given": "Per", "initials": "P"}, {"family": "Schmidt", "given": "Alexej", "initials": "A", "orcid": "0000-0002-1185-3012", "researcher": {"href": "https://publications.scilifelab.se/researcher/3708b225fbae4c239bdc3bea34beff17.json"}}, {"family": "Mu", "given": "Yabing", "initials": "Y", "orcid": "0000-0003-3193-1425", "researcher": {"href": "https://publications.scilifelab.se/researcher/626d44f4c6d7498ea7e2690e9f7008d5.json"}}, {"family": "Zang", "given": "Guangxiang", "initials": "G"}, {"family": "Song", "given": "Jie", "initials": "J", "orcid": "0000-0002-4955-9118", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfb760d62cfc4eda9e18a6d618345334.json"}}, {"family": "Gajavilli", "given": "Vishnupriya", "initials": "V"}, {"family": "Tao", "given": "Junting", "initials": "J"}, {"family": "Rakhimova", "given": "Olena", "initials": "O", "orcid": "0000-0002-3536-4467", "researcher": {"href": "https://publications.scilifelab.se/researcher/727f418f4ea24859ba4bf0e4bdf1f64c.json"}}, {"family": "Ericsson", "given": "Madelene", "initials": "M"}, {"family": "Aripaka", "given": "Karthik", "initials": "K", "orcid": "0000-0001-5071-6187", "researcher": {"href": "https://publications.scilifelab.se/researcher/2622fdbe964f4f99810cdc20c67a9fe0.json"}}, {"family": "Halin Bergstr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Yuan", "given": "Wei", "initials": "W"}, {"family": "Bogdan", "given": "Denisa", "initials": "D"}, {"family": "Zhang", "given": "Aaron Huairen", "initials": "AH"}, {"family": "Welti", "given": "Jon", "initials": "J"}, {"family": "Bergh", "given": "Anders", "initials": "A", "orcid": "0000-0001-5163-5821", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba7945f3e27f4628ba29c7003b3bdf36.json"}}, {"family": "de Bono", "given": "Johann", "initials": "J"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH", "orcid": "0000-0002-9508-896X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f705f7c509904a1db721ace2267ca48f.json"}}, {"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": "2026-06-17", "journal": {"title": "Signal Transduct Target Ther", "issn": "2059-3635", "volume": "11", "issue": "1", "issn-l": null}, "abstract": "Metastatic castration-resistant prostate cancer (mCRPC) remains the primary cause of prostate cancer-related mortality. Despite the availability of treatments, the molecular mechanisms underlying tumor invasion and metastasis are not fully understood, highlighting the need for novel therapeutic strategies. In this study, we developed fully human monoclonal antibodies (mAbs) that prevent the proteolytic cleavage of the transforming growth factor-beta (TGF\u03b2) type I receptor (T\u03b2RI) by steric hindrance. This cleavage, mediated by the metalloprotease ADAM17 (a disintegrin and metalloprotease domain 17; also known as TACE), results in the generation of a soluble intracellular domain (T\u03b2RI-ICD) that is translocated to the nucleus of castration-resistant prostate cancer (CRPC) cells and promotes epithelial-to-mesenchymal transition (EMT), invasion, and metastasis. High levels of TGFBR1 correlated with poor survival in two independent clinical cohorts of patients with mCRPC, and a strong positive correlation between TGFBR1 and ADAM17 expression was observed. In a preclinical human orthotopic mCRPC mouse model, treatment with therapeutic mAbs effectively prevented the nuclear accumulation of T\u03b2RI-ICD, inhibited EMT, and suppressed tumor growth, invasion, and metastasis. Notably, the therapeutic effect was comparable to that of docetaxel, a current standard-of-care chemotherapy, without noticeable side effects on body weight, proximal aorta or heart function detected in immune-deficient mice. These findings suggest that targeting T\u03b2RI cleavage using specific mAbs is a novel precision medicine approach for the treatment of mCRPC. By selectively blocking the prometastatic activity of T\u03b2RI-ICD without disrupting physiological TGF\u03b2 signaling, this strategy may provide a safer and more effective alternative to existing therapies for advanced prostate cancer.", "doi": "10.1038/s41392-026-02737-x", "pmid": "42303991", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41392-026-02737-x"}, {"db": "pmc", "key": "PMC13272619"}], "notes": [], "created": "2026-06-29T07:17:03.522Z", "modified": "2026-07-06T20:10:17.411Z"}, {"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"}]}