REST is a crucial regulator for acquiring EMT-like and stemness phenotypes in hormone-refractory prostate cancer

Yi Ting Chang, Tzu Ping Lin, Mel Campbell, Chin Chen Pan, Shu Hui Lee, Hsin Chen Lee, Muh Hwa Yang, Hsing Jien Kung, Pei Ching Chang

研究成果: 雜誌貢獻文章同行評審

18 引文 斯高帕斯(Scopus)

摘要

Castration-resistance prostate cancer (CRPC), also known as hormone-refractory prostate cancer (HRPC), requires immediate attention since it is not only resistant to androgen ablation, chemo-and radiotherapy, but also highly metastatic. Increasing evidence suggests that enrichment of neuroendocrine (NE) cells is associated with CRPC. Here, combined RNA-seq and ChIP-seq analysis reveals that REST is involved in epithelial-mesenchymal transition (EMT) and stemness acquisition in NE differentiated prostate cancer (PCa) cells via direct transcriptional repression of Twist1 and CD44. Specifically we show that short-term knockdown of REST induces NE differentiation of LNCaP cells. Long-term REST knockdown enhanced the expression of Twist1 and CD44, cell migration and sphere formation. Overexpression of REST in hormone-refractory CWR22Rv1 PCa cells significantly reduces Twist1 and CD44 expression, cell migration and sphere formation. Collectively, our study uncovers REST in regulating EMT and stemness properties of NE PCa cells and suggests that REST is a potential therapeutic target for CRPC.
原文英語
文章編號42795
期刊Scientific Reports
7
DOIs
出版狀態已發佈 - 三月 3 2017

ASJC Scopus subject areas

  • General

指紋 深入研究「REST is a crucial regulator for acquiring EMT-like and stemness phenotypes in hormone-refractory prostate cancer」主題。共同形成了獨特的指紋。

引用此