Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments

Patrick T. Caswell, Heather J. Spence, Maddy Parsons, Dominic P. White, Katherine Clark, Kwai Wa Cheng, Gordon B. Mills, Martin J. Humphries, Anthea J. Messent, Kurt I. Anderson, Mary W. McCaffrey, Bradford W. Ozanne, Jim C. Norman

    Research output: Contribution to journalArticle

    300 Scopus citations

    Abstract

    Here, we report a direct interaction between the β1 integrin cytoplasmic tail and Rab25, a GTPase that has been linked to tumor aggressiveness and metastasis. Rab25 promotes a mode of migration on 3D matrices that is characterized by the extension of long pseudopodia, and the association of the GTPase with α5β1 promotes localization of vesicles that deliver integrin to the plasma membrane at pseudopodial tips as well as the retention of a pool of cycling α5β1 at the cell front. Furthermore, Rab25-driven tumor-cell invasion into a 3D extracellular matrix environment is strongly dependent on ligation of fibronectin by α5β1 integrin and the capacity of Rab25 to interact with β1 integrin. These data indicate that Rab25 contributes to tumor progression by directing the localization of integrin-recycling vesicles and thereby enhancing the ability of tumor cells to invade the extracellular matrix.

    Original languageEnglish (US)
    Pages (from-to)496-510
    Number of pages15
    JournalDevelopmental Cell
    Volume13
    Issue number4
    DOIs
    StatePublished - Oct 9 2007

    Keywords

    • CELLBIO

    ASJC Scopus subject areas

    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Developmental Biology
    • Cell Biology

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  • Cite this

    Caswell, P. T., Spence, H. J., Parsons, M., White, D. P., Clark, K., Cheng, K. W., Mills, G. B., Humphries, M. J., Messent, A. J., Anderson, K. I., McCaffrey, M. W., Ozanne, B. W., & Norman, J. C. (2007). Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments. Developmental Cell, 13(4), 496-510. https://doi.org/10.1016/j.devcel.2007.08.012