ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Cancer Cell Biology

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1598400

This article is part of the Research TopicThe Ubiquitin-Proteasome System and Cellular Signaling: Mechanisms and Regulatory Roles in Cancer and Infectious Diseases.View all articles

ELOVL2 Mediated Stabilization of AR Contributes to Enzalutamide Resistance in Prostate Cancer

Provisionally accepted
Jinpeng CenJinpeng Cen1Jiading GuoJiading Guo2Xianzi ZengXianzi Zeng3Xianlu SongXianlu Song2Shengdong GeShengdong Ge1Mingkun ChenMingkun Chen4Qianyi LiQianyi Li5Yuzhong YuYuzhong Yu1*Daojun LvDaojun Lv6*Shanchao ZhaoShanchao Zhao1,3*
  • 1Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
  • 2Guangzhou Medical University Cancer Hospital, Guangzhou, Guangdong Province, China
  • 3Department of Urology, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, China
  • 4Department of Urology, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
  • 5Southern Medical University, Guangzhou, Guangdong, China
  • 6Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

Androgen receptor (AR) inhibitor enzalutamide represents the cornerstone therapeutic approach for castration-resistant prostate cancer (CRPC). Nevertheless, the frequent emergence of resistance to this treatment remains a significant clinical challenge, with the underlying molecular mechanisms not yet fully understood.Through comprehensive bioinformatic analysis of LNCaP/enzalutamide-resistant cells, we identified that the activation of fatty acid metabolism, specifically through the upregulation of the elongation of very-long chain fatty acid protein 2 (ELOVL2), plays a pivotal role in promoting enzalutamide resistance. Notably, targeted inhibition of ELOVL2 not only suppressed cancer cell proliferation but also restored enzalutamide sensitivity in resistant PCa cells. Mechanistically, ELOVL2 facilitates enzalutamide resistance by impairing the ubiquitin-proteasome system, leading to the subsequent activation of AR signaling pathways. Collectively, our findings suggest that pharmacological inhibition of ELOVL2 may represent a promising novel therapeutic strategy for overcoming enzalutamide resistance in PCa patients.

Keywords: ELOVL2, enzalutamide resistance, androgen receptor, prostate cancer, crpc

Received: 23 Mar 2025; Accepted: 23 May 2025.

Copyright: © 2025 Cen, Guo, Zeng, Song, Ge, Chen, Li, Yu, Lv and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yuzhong Yu, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China
Daojun Lv, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong Province, China
Shanchao Zhao, Department of Urology, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material