β-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells

Timothy T. Li, Mistre Alemayehu, Adel I. Aziziyeh, Cynthia Pape, Macarena Pampillo, Lynne Marie Postovit, Gordon Mills, Andy V. Babwah, Moshmi Bhattacharya

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    Abstract

    The lipid mediator lysophosphatidic acid (LPA) plays a role in cancer progression and signals via specific G protein-coupled receptors, LPA1-3.LPA has been shown to enhance the metastasis of breast carcinoma cells to bone. However, the mechanisms by which LPA receptors regulate breast cancer cell migration and invasion remain unclear. Breast cancer cell proliferation has been shown to be stimulated by Ral GTPases, amember of the Ras superfamily. Ral activity can be regulated by the multifunctional protein â-arrestin.We now show that HS578T and MDA-MB-231 breast cancer cells and MDA-MB-435 melanoma cells have higher expression of â-arrestin 1 mRNA compared with the nontumorigenic mammary MCF-10A cells.Moreover, we found that the mRNA levels of LPA1, LPA2, â-arrestin 2, and Ral GTPases are elevated in the advanced stages of breast cancer.LPA stimulates the migration and invasion of MDA-MB-231 cells, but not of MCF-10A cells, and this is mediated by pertussis toxin-sensitive G proteins and LPA1. However, ectopic expression of LPA1 in MCF-10A cells caused these cells to acquire an invasive phenotype.Ge ne knockdown of either â-arrestin or Ral proteins significantly impaired LPA-stimulated migration and invasion.Th us, our data show a novel role for â-arrestin/Ral signaling in mediating LPA-induced breast cancer cell migration and invasion, two important processes in metastasis.

    Original languageEnglish (US)
    Pages (from-to)1064-1077
    Number of pages14
    JournalMolecular Cancer Research
    Volume7
    Issue number7
    DOIs
    StatePublished - Jul 1 2009

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    ASJC Scopus subject areas

    • Molecular Biology
    • Oncology
    • Cancer Research

    Cite this

    Li, T. T., Alemayehu, M., Aziziyeh, A. I., Pape, C., Pampillo, M., Postovit, L. M., Mills, G., Babwah, A. V., & Bhattacharya, M. (2009). β-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells. Molecular Cancer Research, 7(7), 1064-1077. https://doi.org/10.1158/1541-7786.MCR-08-0578