Noncanonical functions of UGT2B17 promote castration-resistant prostate cancer progression

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.

Authors

Institutions

Publication Details

Journal
Journal of Clinical Investigation
Published
2025-12-04
DOI
https://doi.org/10.1172/jci196495
Primary Topic
Prostate Cancer Treatment and Research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Noncanonical functions of UGT2B17 promote castration-resistant prostate cancer progression

Qiongqiong Jia, Éric Lévesque, Nathan A. Lack, Sonia H.Y. Kung et al.
Journal of Clinical Investigation
Prostate Cancer Treatment and Research
article

Noncanonical functions of UGT2B17 promote castration-resistant prostate cancer progression

Qiongqiong Jia, Éric Lévesque, Nathan A. Lack, Sonia H.Y. Kung, Jianfei Qi, Bo Han, Ladan Fazli, Tunç Morova, Tingting Feng, Xuesen Dong, Lin Gao, Chantal Guillemette, Louis Lacombe, Lin Wang, Yinan Li, Ning Xie
article en

Abstract

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.

Journal of Clinical InvestigationVol. 136(2)
University of Maryland, Baltimore (US), Koç University (TR), University of British Columbia (CA), Shandong University (CN), Shanghai Jiao Tong University (CN), Peking University (CN), Renji Hospital (CN), Vancouver General Hospital (CA), Faculty (United Kingdom) (GB), Centre hospitalier universitaire de Québec (CA), Peking University People's Hospital (CN), Centre hospitalier de l'Université Laval (CA), Shandong First Medical University (CN), Université Laval (CA)
Openalex Percentile: Top 43%
Prostate Cancer Treatment and Research
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.