{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:52:18Z","timestamp":1791913938926,"version":"4.3.4"},"reference-count":62,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"29","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,7,22]]},"abstract":"<jats:p>\n            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\n            <jats:sup>(i)pe\u2212\/\u2212<\/jats:sup>\n            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 progression-free survival after prostatectomy. Last, we show that pharmacologically inhibiting HIF1A impairs cell proliferation and induces apoptosis in PINs. Therefore, our study demonstrates that HIF1A is a target for PCa prevention and that TGM2 is a promising prognostic biomarker of early relapse after prostatectomy.\n          <\/jats:p>","DOI":"10.1126\/sciadv.abo2295","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T17:58:21Z","timestamp":1658512701000},"source":"Crossref","is-referenced-by-count":51,"title":["Hypoxia-mediated stabilization of HIF1A in prostatic intraepithelial neoplasia promotes cell plasticity and malignant progression"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-6376","authenticated-orcid":true,"given":"Mohamed A.","family":"Abu el Maaty","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Illkirch, France."},{"name":"Centre National de la Recherche Scientifique (CNRS), UMR7104, Illkirch, France."},{"name":"Institut National de la Sant\u00e9 et de la Recherche 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