Yin Yang 1 promotes the neuroendocrine differentiation of prostate cancer cells via the non-canonical WNT pathway (FYN/STAT3)

A growing number of studies have shown that Yin Yang 1 (YY1) promotes the development of multiple tumours. The purpose of the current study was to determine the mechanism by which YY1 mediates neuroendocrine differentiation of prostate cancer (NEPC) cells undergoing cellular plasticity. Using the Ca...

Full description

Saved in:
Bibliographic Details
Published in:Clinical and translational medicine 2023-10, Vol.13 (10), p.e1422-n/a
Main Authors: Liu, Rui-Ji, Xu, Zhi-Peng, Huang, Xiang, Xu, Bin, Chen, Ming
Format: Article
Language:English
Subjects:
Androgen Antagonists
Androgens
Cell Differentiation - genetics
Cell growth
cellular lineage plasticity
Clinical medicine
Cloning
EMT
Epigenetics
FZD8
Genomes
Humans
Male
Metastasis
neuroendocrine differentiation of prostate cancer
Prostate cancer
Prostatic Neoplasms - metabolism
Protein expression
Proteins
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
Wnt Signaling Pathway - genetics
Wound healing
Yin-Yang
YY1
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:A growing number of studies have shown that Yin Yang 1 (YY1) promotes the development of multiple tumours. The purpose of the current study was to determine the mechanism by which YY1 mediates neuroendocrine differentiation of prostate cancer (NEPC) cells undergoing cellular plasticity. Using the Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases, we bioinformatically analyzed YY1 expression in prostate cancer (PCa). Aberrant YY1 expression was validated in different PCa tissues and cell lines via quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemistry. In vivo and in vitro functional assays verified the oncogenicity of YY1 in PCa. Further functional assays showed that ectopic expression of YY1 promoted cellular plasticity in PCa cells via epithelial-mesenchymal transition induction and neuroendocrine differentiation. Androgen deprivation therapy induced a decrease in YY1 protein ubiquitination, enhanced its stability, and thus enhanced the transcriptional activity of FZD8. Castration enhanced FZD8 binding to Wnt9A and mediated cellular plasticity by activating the non-canonical Wnt (FZD8/FYN/STAT3) pathway. We identified YY1 as a novel dysregulated transcription factor that plays an important role in NEPC progression in this study. We believe that an in-depth investigation of the mechanism underlying YY1-mediated disease may lead to improved NEPC therapies.
ISSN:2001-1326
2001-1326
DOI:10.1002/ctm2.1422