ROCK cooperated with ET-1 to induce epithelial to mesenchymal transition through SLUG in human ovarian cancer cells

Biosci Biotechnol Biochem. 2012;76(1):42-7. doi: 10.1271/bbb.110411. Epub 2012 Jan 7.

Abstract

The Rho-associated serine-threonine protein kinase (ROCK) is a downstream effector of Rho GTPases that is frequently activated in the epithelial to mesenchymal transition (EMT) of human ovarian cancer cells. On the other hand, endothelin-1 (ET-1) and its receptor endothelin A receptor (ET(A)R) are overexpressed in primary and metastatic ovarian carcinoma, which suggests that ET-1 promotes tumor dissemination. Hence, two human ovarian carcinoma cell lines, SK-OV-3 and CaOV3, were chosen to study the effects of ET-1/ET(A)R and ROCK in promoting EMT of ovarian cancer cells. We found that ET-1 exposure induced EMT of SK-OV-3 and CaOV3 by monitoring cells morphology, enhanced fibronectin, and reduced E-cadherin protein. At the same time, ET-1/ET(A)R enhanced the level of transcription of SLUG a transcriptional repressor of E-cadherin. More importantly, a constitutively active mutant of ROCK enhanced the transcription of SLUG by stimulating SLUG promoter activity. Furthermore, ROCK inhibitor Y27632 reversed the increase in fibronectin induced by ET-1/ET(A)R. Our data suggest that ROCK cooperated with ET-1/ET(A)R to promote EMT of human ovarian carcinoma cells through upregulation of SLUG mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics
  • Cell Line, Tumor
  • Endothelin-1 / metabolism*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Ovarian Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Endothelin A / metabolism
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Up-Regulation
  • rho-Associated Kinases / metabolism*

Substances

  • Cadherins
  • Endothelin-1
  • RNA, Messenger
  • Receptor, Endothelin A
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • rho-Associated Kinases