Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines

Cell Biol Toxicol. 2010 Dec;26(6):553-67. doi: 10.1007/s10565-010-9163-5. Epub 2010 Apr 16.

Abstract

The epithelial-mesenchymal transition (EMT) is regarded as an important step in cancer metastasis. Snail, a master regulator of EMT, has been recently proposed to act additionally as a cell survival factor and inducer of motility. We have investigated the function of Snail (SNAI1) in prostate cancer cells by downregulating its expression via short (21-mer) interfering RNA (siRNA) and measuring the consequences on EMT markers, cell viability, death, cell cycle, senescence, attachment, and invasivity. Of eight carcinoma cell lines, the prostate carcinoma cell lines LNCaP and PC-3 showed the highest and moderate expression of SNAI1 mRNA, respectively, as measured by quantitative RT-PCR. Long-term knockdown of Snail induced a severe decline in cell numbers in LNCaP and PC-3 and caspase activity was accordingly enhanced in both cell lines. In addition, suppression of Snail expression induced senescence in LNCaP cells. SNAI1-siRNA-treated cells did not tolerate detachment from the extracellular matrix, probably due to downregulation of integrin α6. Expression of E-cadherin, vimentin, and fibronectin was also affected. Invasiveness of PC-3 cells was not significantly diminished by Snail knockdown. Our data suggest that Snail acts primarily as a survival factor and inhibitor of cellular senescence in prostate cancer cell lines. We therefore propose that Snail can act as early driver of prostate cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / genetics
  • Cellular Senescence / genetics*
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alpha6 / metabolism
  • Male
  • Neoplasm Metastasis
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Integrin alpha6
  • RNA, Messenger
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors