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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number42795
JournalScientific Reports
Volume7
DOIs
StatePublished - Mar 3 2017

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Epithelial-Mesenchymal Transition
Prostatic Neoplasms
Hormones
Phenotype
Castration
Cell Movement
Neuroendocrine Cells
Androgens
Cell Differentiation
Radiotherapy
RNA

ASJC Scopus subject areas

  • General

Cite this

REST is a crucial regulator for acquiring EMT-like and stemness phenotypes in hormone-refractory prostate cancer. / Chang, Yi Ting; Lin, Tzu Ping; Campbell, Mel; Pan, Chin Chen; Lee, Shu Hui; Lee, Hsin Chen; Yang, Muh Hwa; Kung, Hsing Jien; Chang, Pei Ching.

In: Scientific Reports, Vol. 7, 42795, 03.03.2017.

Research output: Contribution to journalArticle

Chang, Yi Ting ; Lin, Tzu Ping ; Campbell, Mel ; Pan, Chin Chen ; Lee, Shu Hui ; Lee, Hsin Chen ; Yang, Muh Hwa ; Kung, Hsing Jien ; Chang, Pei Ching. / REST is a crucial regulator for acquiring EMT-like and stemness phenotypes in hormone-refractory prostate cancer. In: Scientific Reports. 2017 ; Vol. 7.
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AU - Kung, Hsing Jien

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