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

Sci Rep. 2017 Mar 3;7:42795. doi: 10.1038/srep42795.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement
  • Chromatin Immunoprecipitation
  • Epigenesis, Genetic
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics*
  • Male
  • Nuclear Proteins / genetics*
  • Phenotype
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Repressor Proteins / genetics*
  • Sequence Analysis, RNA
  • Twist-Related Protein 1 / genetics*


  • CD44 protein, human
  • Hyaluronan Receptors
  • Nuclear Proteins
  • RE1-silencing transcription factor
  • Repressor Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1