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

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 rol...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular and molecular medicine 2020-10, Vol.24 (20), p.12032-12043
Main Authors: Wang, Bin, Wu, Shiqi, Fang, Yong, Sun, Guangxi, He, Dalin, Hsieh, Jer‐Tsong, Wang, Xinyang, Zeng, Hao, Wu, Kaijie
Format: Article
Language:English
Subjects:
Aged
AKR1C3
Aldo-Keto Reductase Family 1 Member C3 - metabolism
Alternative splicing
Androgen receptors
Androgens
Animals
Antibodies
AR‐V7
B4GALT1
Cancer therapies
Castration
castration‐resistant prostate cancer
Cell Line, Tumor
Cell Proliferation
complex
Galactosyltransferases - genetics
Galactosyltransferases - metabolism
Gene Expression Regulation, Neoplastic
HEK293 Cells
Humans
Male
Medical prognosis
Metastases
Metastasis
Mice, Inbred BALB C
Mice, Nude
Models, Biological
Original
Phenols
Plasmids
Prostate
Prostate cancer
Prostatic Neoplasms, Castration-Resistant - genetics
Prostatic Neoplasms, Castration-Resistant - pathology
Protein Binding
Protein Stability
Proteins
Receptors, Androgen - genetics
Transcription, Genetic
Tumors
Ubiquitin - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.15831