EGFR mediates LPA-induced proteolytic enzyme expression and ovarian cancer invasion: inhibition by resveratrol

Mol Oncol. 2013 Feb;7(1):121-9. doi: 10.1016/j.molonc.2012.10.001. Epub 2012 Oct 23.


Lysophosphatidic acid (LPA) augments proliferation and metastasis of various cancer cells. We recently identified a critical role of the Rho/ROCK pathway for LPA-induced proteolytic enzyme expression and cancer cell progression. In the present study, we elucidate the underlying mechanisms by which LPA induces Rho activation and subsequent cellular invasion, and the reversal of these effects by resveratrol. We observed that both Gi and G13 contribute to LPA-induced EGFR activation. The activated EGFR in turn initiates a Ras/Rho/ROCK signaling cascade, leading to proteolytic enzyme secretion. Further we provide evidence that resveratrol inhibits EGFR phosphorylation and subsequent activation of a Ras/Rho/ROCK signaling. Therefore, we demonstrate a mechanistic cascade of LPA activating EGFR through Gi and G13 thus inducing a Ras/Rho/ROCK signaling for proteolytic enzyme expression and ovarian cancer cell invasion, as well as interference of the cascade by resveratrol through blocking EGFR phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Lysophospholipids / pharmacology*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Phosphorylation / drug effects
  • Resveratrol
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stilbenes / pharmacology*


  • Lysophospholipids
  • Stilbenes
  • EGFR protein, human
  • ErbB Receptors
  • lysophosphatidic acid
  • Resveratrol