Open AccessThe AKR1C3/AR‐V7 complex maintains CRPC tumour growth by repressing B4GALT1 expression
Author(s) -
Wang Bin,
Wu Shiqi,
Fang Yong,
Sun Guangxi,
He Dalin,
Hsieh JerTsong,
Wang Xinyang,
Zeng Hao,
Wu Kaijie
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15831
Subject(s) - prostate cancer , androgen receptor , cancer research , suppressor , coactivator , biology , androgen , in vivo , cancer , gene , endocrinology , transcription factor , genetics , hormone
Multiple mechanisms contribute to the survival and growth of metastatic castration‐resistant prostate cancer (mCRPC) cells without androgen, including androgen receptor splice variants (AR‐V) and de novo intratumoral androgen synthesis. AKR1C3 is a critical androgenic enzyme that plays different roles in mCRPC, such as an EMT driver or AR coactivator. However, the relationship and regulatory mechanisms between AKR1C3 and AR‐V remain largely unknown. In this study, we observed a positive correlation between AKR1C3 and AR‐V7 staining in tissues from prostate rebiopsy at mCRPC. Mechanistically, AKR1C3 interacts with AR‐V7 protein in CRPC cells, which can reciprocally inhibit AR‐V7 and AKR1C3 protein degradation. Biologically, this complex is essential for in vitro and in vivo tumour growth of CRPC cells after androgen deprivation as it represses B4GALT1, a unique tumour suppressor gene in PCa. Together, this study reveals AKR1C3/AR‐V7 complex as a potential therapeutic target in mCRPC.