Increased ABCC4 Expression Induced by ERRα Leads to Docetaxel Resistance via Efflux of Docetaxel in Prostate Cancer

Houbao Huang1, Jing Li2, Jing Shen3,4

  • 1Department of Urology, Yijishan Affiliated Hospital, Wannan Medical College, Wuhu, China.

Frontiers in Oncology
|October 5, 2020
PubMed

Insights

Estrogen receptor-related receptor alpha (ERRα) drives docetaxel resistance in prostate cancer (PCa) by targeting ABCC4. Targeting ERRα may overcome drug resistance in PCa patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Docetaxel is a primary treatment for advanced prostate cancer (PCa).
  • Docetaxel resistance significantly limits its clinical efficacy.
  • Estrogen receptor-related receptor alpha (ERRα) is implicated in various cancers.

Purpose of the Study:

  • To investigate the role of ERRα in docetaxel resistance in PCa.
  • To identify molecular mechanisms linking ERRα to docetaxel resistance.
  • To evaluate ERRα as a potential therapeutic target for drug-resistant PCa.

Main Methods:

  • Prostate cancer cell line experiments involving ERRα overexpression and knockdown.
  • Gene expression analysis of ERRα and ABCC4.
  • Chromatin immunoprecipitation (CHIP) and luciferase assays to determine gene targeting.
  • Bioinformatics analysis of ERRα and ABCC4 expression in PCa patients.

Main Results:

  • ERRα overexpression conferred docetaxel resistance, while its downregulation increased sensitivity.
  • ABCC4 expression was synchronously regulated by ERRα.
  • ERRα directly targets ABCC4, leading to its overexpression in resistant cells.
  • ERRα knockdown reversed docetaxel resistance and restored drug accumulation.

Conclusions:

  • ERRα plays a critical role in mediating docetaxel resistance in prostate cancer.
  • ERRα directly targets ABCC4, contributing to drug resistance.
  • ERRα represents a promising therapeutic target for overcoming docetaxel resistance in PCa.

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