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ResearchIn-Press PreviewClinical ResearchOncology Open Access | 10.1172/JCI196495

Non-canonical functions of UGT2B17 promote castrate-resistant prostate cancer progression

Tingting Feng,1 Ning Xie,2 Lin Gao,3 Qiongqiong Jia,2 Sonia Kung,2 Tunc Morova,2 Yinan Li,4 Lin Wang,1 Ladan Fazli,2 Louis Lacombe,5 Chantal Guillemette,6 Eric Lévesque,7 Nathan A. Lack,2 Jianfei Qi,8 Bo Han,9 and Xuesen Dong2

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Feng, T. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Xie, N. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Gao, L. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Jia, Q. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Kung, S. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Morova, T. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Li, Y. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Wang, L. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Fazli, L. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Lacombe, L. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Guillemette, C. in: PubMed | Google Scholar |

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Lévesque, E. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Lack, N. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Qi, J. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Han, B. in: PubMed | Google Scholar

1Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

2The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, Canada

3Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China

4Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

5Faculty of Medicine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

6Faculty of Pharmacy, Université Laval, Centre de recherche du Centre 11 Hospitalier Universitaire de Québec - Université Laval (CRCHUQc-UL), Québec, Canada

7Centre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval (CRCHUQc- UL), Centre de recherche sur le cancer (CRC) de l'Université Laval, Faculty of Medicine, Université Laval, Québec, Canada

8Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, United States of America

9Department of Pathology, Peking University People's Hospital, Beijing, China

Find articles by Dong, X. in: PubMed | Google Scholar |

Published December 4, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI196495.
Copyright © 2025, Feng et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published December 4, 2025 - Version history
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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 2B17 (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 reduces 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.

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  • Version 1 (December 4, 2025): In-Press Preview
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