Ovarian cancer G protein coupled receptor 1 suppresses cell migration of MCF7 breast cancer cells via a Gα12/13-Rho-Rac1 pathway

Jing Li, Bin Guo, Jing Wang, Xiaoyan Cheng, Yan Xu, Jianli Sang

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background: Ovarian cancer G protein coupled receptor 1 (OGR1) mediates inhibitory effects on cell migration in human prostate and ovarian cancer cells. However, the mechanisms and signaling pathways that mediate these inhibitory effects are essentially unknown. Methods: MCF7 cell line was chosen as a model system to study the mechanisms by which OGR1 regulates cell migration, since it expresses very low levels of endogenous OGR1. Cell migratory activities were assessed using both wound healing and transwell migration assays. The signaling pathways involved were studied using pharmacological inhibitors and genetic forms of the relevant genes, as well as small G protein pull-down activity assays. The expression levels of various signaling molecules were analyzed by Western blot and quantitative PCR analysis. Results: Over-expression of OGR1 in MCF7 cells substantially enhanced activation of Rho and inhibition of Rac1, resulting in inhibition of cell migration. In addition, expression of the Gα12/13 specific regulator of G protein signaling (RGS) domain of p115RhoGEF, but not treatment with pertussis toxin (PTX, a Gαi specific inhibitor), could abrogate OGR1-dependent Rho activation, Rac1 inactivation, and inhibition of migration in MCF7 cells. The bioactive lipids tested had no effect on OGR1 function in cell migration. Conclusion: Our data suggest, for the first time, that OGR1 inhibits cell migration through a Gα12/13 -Rho-Rac1 signaling pathway in MCF7 cells. This pathway was not significantly affected by bioactive lipids and all the assays were conducted at constant pH, suggesting a constitutive activity of OGR1. This is the first clear delineation of an OGR1-mediated cell signaling pathway involved in migration.

Original languageEnglish (US)
Article number6
JournalJournal of Molecular Signaling
Volume8
DOIs
StatePublished - May 10 2013

Keywords

  • Cell migration
  • Gα12/13
  • MCF7 cells
  • OGR1
  • Rac1
  • Rho

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

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