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J Cell Sci. 2014 Dec 15;127(Pt 24):5303-16. doi: 10.1242/jcs.157560. Epub 2014 Oct 29.

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

Author information

1
Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XR Edinburgh, UK.
2
Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
3
Cancer Research UK Growth Factor Signalling Group, School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
4
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
5
Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XR Edinburgh, UK m.frame@ed.ac.uk.

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.

KEYWORDS:

Actin; Autophagy; Eps8; FAK; Invasion; Src

PMID:
25359883
PMCID:
PMC4265741
DOI:
10.1242/jcs.157560
[Indexed for MEDLINE]
Free PMC Article

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