{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8(29)"],"submitter":["Abu El Maaty MA"],"pubmed_abstract":["Prostate cancer (PCa) is a leading cause of cancer-related deaths. The slow evolution of precancerous lesions to malignant tumors provides a broad time frame for preventing PCa. To characterize prostatic intraepithelial neoplasia (PIN) progression, we conducted longitudinal studies on Pten<sup>(i)pe-/-</sup> mice that recapitulate prostate carcinogenesis in humans. We found that early PINs are hypoxic and that hypoxia-inducible factor 1 alpha (HIF1A) signaling is activated in luminal cells, thus enhancing malignant progression. Luminal HIF1A dampens immune surveillance and drives luminal plasticity, leading to the emergence of cells that overexpress Transglutaminase 2 (TGM2) and have impaired androgen signaling. Elevated TGM2 levels in patients with PCa are associated with shortened progre"],"journal":["Science advances"],"pagination":["eabo2295"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9307253"],"repository":["biostudies-literature"],"pubmed_title":["Hypoxia-mediated stabilization of HIF1A in prostatic intraepithelial neoplasia promotes cell plasticity and malignant progression."],"pmcid":["PMC9307253"],"pubmed_authors":["Namer IJ","Rovito D","Lutzing R","Grelet E","Lindner V","Metzger D","Terzic J","Yanushko D","Laverny G","Abu El Maaty MA","Parisotto M","Keime C"],"additional_accession":[]},"is_claimable":false,"name":"Hypoxia-mediated stabilization of HIF1A in prostatic intraepithelial neoplasia promotes cell plasticity and malignant progression.","description":"Prostate cancer (PCa) is a leading cause of cancer-related deaths. The slow evolution of precancerous lesions to malignant tumors provides a broad time frame for preventing PCa. To characterize prostatic intraepithelial neoplasia (PIN) progression, we conducted longitudinal studies on Pten<sup>(i)pe-/-</sup> mice that recapitulate prostate carcinogenesis in humans. We found that early PINs are hypoxic and that hypoxia-inducible factor 1 alpha (HIF1A) signaling is activated in luminal cells, thus enhancing malignant progression. Luminal HIF1A dampens immune surveillance and drives luminal plasticity, leading to the emergence of cells that overexpress Transglutaminase 2 (TGM2) and have impaired androgen signaling. Elevated TGM2 levels in patients with PCa are associated with shortened progre","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-04-22T11:27:14.963Z","creation":"2025-04-05T23:59:23.176Z"},"accession":"S-EPMC9307253","cross_references":{"pubmed":["35867798"],"doi":["10.1126/sciadv.abo2295"]}}