Epidermal Growth Factor Receptor substrate 8 (Eps8) controls Src/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

Research output: Contribution to journalArticlepeer-review

Abstract

Eps8 is an actin regulatory scaffold protein increased in Squamous Cell Carcinoma (SCC) cells. It forms a complex with both Focal Adhesion Kinase (FAK) and c-Src in SCC cells derived from the DMBA/TPA model of skin carcinogenesis. Here, we describe two new roles for Eps8. Firstly, it controls the spatial distribution of active c-Src in a FAK-dependent manner. Specifically, Eps8 participates in, and regulates, a biochemical complex with c-Src and drives c-Src's trafficking to autophagic structures that SCC cells use to cope with high levels of active c-Src when FAK is absent. Secondly, when FAK is expressed in SCC cells, so tethering active c-Src at focal adhesion complexes, Eps8 is also recruited to focal adhesions and is required for FAK-dependent polarization and invasion. Therefore, Eps8 is a critical mediator of Src/FAK-regulated processes; it participates in specific biochemical complexes and promotes actin re-arrangements that determine c-Src's spatial localization and Src/FAK functions in invasive migration.

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

Keywords

  • Eps8
  • FAK
  • Invasion
  • Autophagy
  • Src
  • Actin
  • FOCAL ADHESION KINASE
  • CANCER-CELLS
  • MEDIATED TRANSFORMATION
  • V-SRC
  • PROTEIN
  • EXPRESSION
  • INHIBITOR
  • MIGRATION
  • SURVIVAL
  • COMPLEX

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