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

Kang Jin Jeong, Kyung Hwa Cho, Nattapon Panupinthu, Hoon Kim, Jaeku Kang, Chang Gyo Park, Gordon B. Mills, Hoi Young Lee

    Research output: Contribution to journalArticle

    24 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)121-129
    Number of pages9
    JournalMolecular Oncology
    Volume7
    Issue number1
    DOIs
    StatePublished - Feb 2013

    Keywords

    • EGFR
    • Invasion
    • Lysophosphatidic acid
    • Ovarian cancer
    • Resveratrol

    ASJC Scopus subject areas

    • Molecular Medicine
    • Genetics
    • Oncology
    • Cancer Research

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