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The AKR1C3/AR-V7 complex maintains CRPC tumour growth by repressing B4GALT1 expression

Bin Wang1,2, Shiqi Wu1, Yong Fang3

  • 1Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Journal of Cellular and Molecular Medicine
|September 9, 2020
PubMed

Insights

Researchers discovered a new complex between AKR1C3 and androgen receptor splice variant 7 (AR-V7) that drives prostate cancer growth. This AKR1C3/AR-V7 interaction offers a potential therapeutic target for metastatic castration-resistant prostate cancer (mCRPC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Urology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) cells can survive without androgens via mechanisms like androgen receptor splice variants (AR-V) and intratumoral androgen synthesis.
  • AKR1C3, an androgenic enzyme, plays multifaceted roles in mCRPC, including driving epithelial-mesenchymal transition (EMT) and acting as an androgen receptor (AR) coactivator.
  • The precise relationship and regulatory mechanisms between AKR1C3 and AR-V remain largely unelucidated.

Purpose of the Study:

  • To investigate the relationship and regulatory mechanisms between AKR1C3 and androgen receptor splice variants (AR-V) in prostate cancer.
  • To explore the biological significance of the AKR1C3/AR-V interaction in the context of mCRPC.
  • To identify potential therapeutic targets for mCRPC based on the AKR1C3/AR-V axis.

Main Methods:

  • Correlative analysis of AKR1C3 and AR-V7 protein expression in mCRPC patient tissues.
  • Co-immunoprecipitation assays to determine protein-protein interactions between AKR1C3 and AR-V7 in castration-resistant prostate cancer (CRPC) cells.
  • Assessment of the impact of the AKR1C3/AR-V7 complex on tumor growth in vitro and in vivo, and its effect on B4GALT1 expression.

Main Results:

  • A positive correlation was observed between AKR1C3 and AR-V7 staining in mCRPC patient tissues.
  • AKR1C3 directly interacts with AR-V7 protein in CRPC cells, leading to reciprocal inhibition of their protein degradation.
  • The AKR1C3/AR-V7 complex is crucial for CRPC cell growth under androgen deprivation, partly by repressing the tumor suppressor gene B4GALT1.

Conclusions:

  • The study identifies a novel protein complex between AKR1C3 and AR-V7 in mCRPC.
  • This AKR1C3/AR-V7 complex promotes tumor growth in the absence of androgens and warrants further investigation.
  • The AKR1C3/AR-V7 complex represents a promising potential therapeutic target for mCRPC treatment.
Keywords:
AKR1C3AR-V7B4GALT1castration-resistant prostate cancercomplex

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