{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:25:28Z","timestamp":1782854728729,"version":"3.54.5"},"reference-count":49,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["MOP137007"],"award-info":[{"award-number":["MOP137007"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:p>Androgen deprivation therapy is the primary treatment for advanced prostate tumors. While initially effective, tumor progression to the therapy-resistant stage is inevitable. Paradoxically, UDP glucuronosyltransferase family 2 member B17 (UGT2B17), the key enzyme responsible for androgen catabolism in prostate tumor cells, is upregulated in therapy-resistant tumors, though its role in tumor progression remains unclear. Here, we demonstrate that UGT2B17 possesses multiple oncogenic functions independent of androgen catabolism. It modulates protein-folding pathways, allowing tumor cells to endure therapy-induced stress. UGT2B17 also regulates transcription associated with cell division and the DNA damage response, enabling unchecked cell proliferation. Targeting the newly identified UGT2B17 functions using a combination of inhibitors reduced tumor growth in therapy-resistant tumor models, highlighting a promising therapeutic strategy. Collectively, these findings reveal a mechanism by which prostate tumors exploit UGT2B17 to evade therapy and highlight its potential as a therapeutic target in advanced prostate cancer.<\/jats:p>","DOI":"10.1172\/jci196495","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T17:00:18Z","timestamp":1764867618000},"source":"Crossref","is-referenced-by-count":1,"title":["Noncanonical functions of UGT2B17 promote castration-resistant prostate cancer progression"],"prefix":"10.1172","volume":"136","author":[{"given":"Tingting","family":"Feng","sequence":"first","affiliation":[{"name":"Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China."},{"name":"The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Xie","sequence":"additional","affiliation":[{"name":"The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongqiong","family":"Jia","sequence":"additional","affiliation":[{"name":"The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia H.Y.","family":"Kung","sequence":"additional","affiliation":[{"name":"The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunc","family":"Morova","sequence":"additional","affiliation":[{"name":"The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladan","family":"Fazli","sequence":"additional","affiliation":[{"name":"The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1113-1212","authenticated-orcid":true,"given":"Chantal","family":"Guillemette","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Centre de recherche du Centre Hospitalier Universitaire de Qu\u00e9bec - 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