Eps8 controls Src- and FAK-dependent phenotypes in squamous carcinoma cells

Christina Schoenherr, Bryan Serrels, Charlotte Proby, Debbie L. Cunningham, Jane E. Findlay, George S. Baillie, John K. Heath, Margaret C. Frame (Lead / Corresponding author)

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    Abstract

    Eps8 is an actin regulatory scaffold protein whose expression is increased in squamous cell carcinoma (SCC) cells. It forms a complex with both focal adhesion kinase (FAK, also known as PTK2) and Src in SCC cells derived from skin carcinomas induced by administration of the chemical DMBA followed by TPA (the DMBA/TPA model). Here, we describe two new roles for Eps8. Firstly, it controls the spatial distribution of active Src in a FAK-dependent manner. Specifically, Eps8 participates in, and regulates, a biochemical complex with Src and drives trafficking of Src to autophagic structures that SCC cells use to cope with high levels of active Src when FAK is absent. Secondly, when FAK is expressed in SCC cells, thereby meaning active Src becomes tethered at focal adhesion complexes, Eps8 is also recruited to focal adhesions and is required for FAK-dependent polarization and invasion. Therefore, Eps8 is a crucial mediator of Src- and FAK-regulated processes; it participates in specific biochemical complexes and promotes actin re-arrangements that determine the spatial localization of Src, and modulates the functions of Src and FAK during invasive migration.

    Original languageEnglish
    Pages (from-to)5303-5316
    Number of pages14
    JournalJournal of Cell Science
    Volume127
    Issue number24
    Early online date29 Oct 2014
    DOIs
    Publication statusPublished - 15 Dec 2014

    Keywords

    • Actin
    • Autophagy
    • Eps8
    • FAK
    • Invasion
    • Src

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    Cite this

    Schoenherr, C., Serrels, B., Proby, C., Cunningham, D. L., Findlay, J. E., Baillie, G. S., Heath, J. K., & Frame, M. C. (2014). Eps8 controls Src- and FAK-dependent phenotypes in squamous carcinoma cells. Journal of Cell Science, 127(24), 5303-5316. https://doi.org/10.1242/jcs.157560