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Updated: Jan 9, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Noncanonical functions of UGT2B17 promote castration-resistant prostate cancer progression
Tingting Feng1,2, Ning Xie2, Lin Gao3
1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
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.
Insights
UDP-glucuronosyltransferase 2B17 (UGT2B17) promotes advanced prostate tumor growth and therapy resistance through novel oncogenic functions. Inhibiting these functions offers a promising new strategy for treating resistant prostate cancer.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Androgen deprivation therapy (ADT) is standard for advanced prostate cancer, but resistance is inevitable.
- UDP-glucuronosyltransferase 2B17 (UGT2B17), involved in androgen metabolism, is paradoxically upregulated in therapy-resistant tumors.
- The specific role of UGT2B17 in prostate tumor progression and therapy resistance remains largely unknown.
Purpose of the Study:
- To investigate the oncogenic functions of UGT2B17 in advanced prostate tumors beyond androgen catabolism.
- To elucidate the mechanisms by which UGT2B17 contributes to therapy resistance.
- To evaluate UGT2B17 as a potential therapeutic target for resistant prostate cancer.
Main Methods:
- Assessed UGT2B17's role in protein-folding pathways and response to therapy-induced stress.
- Analyzed UGT2B17's regulation of transcription related to cell division and DNA damage response.
- Tested the efficacy of UGT2B17 inhibitors in combination therapy on resistant prostate tumor models.
Main Results:
- UGT2B17 exhibits oncogenic functions independent of androgen catabolism, enhancing tumor cell survival under stress.
- UGT2B17 modulates cell division and DNA damage response pathways, promoting proliferation in resistant tumors.
- Combined inhibition of UGT2B17 functions significantly reduced tumor growth in therapy-resistant models.
Conclusions:
- UGT2B17 plays a critical role in prostate tumor progression and therapy resistance through novel oncogenic mechanisms.
- Targeting UGT2B17's newly identified functions presents a promising therapeutic strategy for advanced, resistant prostate cancer.
- Understanding UGT2B17's multifaceted roles opens new avenues for overcoming treatment resistance in prostate tumors.
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