Involvement of HDAC1 in E-cadherin expression in prostate cancer cells; its implication for cell motility and invasion

Biochem Biophys Res Commun. 2011 Jan 28;404(4):915-21. doi: 10.1016/j.bbrc.2010.12.081. Epub 2010 Dec 22.

Abstract

In this study, we investigate the molecular mechanism by which histone deacetylase (HDAC) inhibitors exert anti-invasiveness effect against prostate cancer cells. We first evaluate the growth inhibition effect of HDAC inhibitors in prostate cancer cells, which is accompanied by induction of p21(WAF1) expression and accumulation of acetylated histones. And we found that the migration and invasion of prostate cancer cells is strongly inhibited by treatment with HDAC inhibitors. In parallel, E-cadherin level is highly up-regulated in HDAC inhibitor-treated prostate cancer cells. And siRNA knockdown of E-cadherin significantly diminishes the anti-invasion effect of HDAC inhibitors, indicating that E-cadherin overexpression is one of possible mechanism for anti-invasion effect of HDAC inhibitors. Furthermore, specific downregulation of HDAC1, but not HDAC2, causes E-cadherin expression and subsequent inhibition of cell motility and invasion. Collectively, our data demonstrate that HDAC1 is a major repressive enzyme for E-cadherin expression as well as HDAC inhibitor-mediated anti-invasiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Antineoplastic Agents / pharmacology*
  • Cadherins / antagonists & inhibitors
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Gene Expression Regulation
  • Histone Deacetylase 1 / antagonists & inhibitors
  • Histone Deacetylase 1 / genetics
  • Histone Deacetylase 1 / metabolism*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Male
  • Neoplasm Invasiveness
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology*
  • RNA, Small Interfering / genetics

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • CDH1 protein, human
  • CDKN1A protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Histone Deacetylase Inhibitors
  • RNA, Small Interfering
  • HDAC1 protein, human
  • Histone Deacetylase 1