Open AccessEGFR mediates LPA‐induced proteolytic enzyme expression and ovarian cancer invasion: Inhibition by resveratrol
Author(s) -
Jeong Kang Jin,
Cho Kyung Hwa,
Panupinthu Nattapon,
Kim Hoon,
Kang Jaeku,
Park Chang Gyo,
Mills Gordon B.,
Lee Hoi Young
Publication year - 2013
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2012.10.001
Subject(s) - lysophosphatidic acid , resveratrol , phosphorylation , microbiology and biotechnology , signal transduction , cancer research , biology , proteolytic enzymes , cancer cell , chemistry , enzyme , cancer , biochemistry , receptor , genetics
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.