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MBC in Press, published online ahead of print February 6, 2008
Mol. Biol. Cell 10.1091/mbc.E07-09-0953

A more recent version of this article appeared on April 1, 2008
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Submitted on September 21, 2007
Revised on January 17, 2008
Accepted on January 30, 2008

A Novel Cas Family Member, HEPL, Regulates FAK and Cell Spreading

Mahendra K. Singh, Disha Dadke, Emmanuelle Nicolas, Ilya G. Serebriiskii, Sinoula Apostolou, Adrian Canutescu, Brian L. Egleston, and Erica A. Golemis

Fox Chase Cancer Center, Philadelphia, PA 19111

Monitoring Editor: Mark Ginsberg

For over a decade, p130Cas/BCAR1, HEF1/NEDD9/Cas-L, and Efs/Sin have defined the Cas scaffolding protein family. Cas proteins mediate integrin-dependent signals at focal adhesions, regulating cell invasion and survival; at least one family member, HEF1, regulates mitosis. We here report a previously undescribed novel branch of the Cas protein family, designated HEPL (for HEF1-Efs-p130Cas-like). The HEPL branch is evolutionarily conserved through jawed vertebrates, and HEPL is found in some species lacking other members of the Cas family. The human HEPL mRNA and protein is selectively expressed in specific primary tissues and cancer cell lines, and HEPL maintains Cas family function in localization to focal adhesions, as well as regulation of FAK activity, focal adhesion integrity, and cell spreading. It has recently been demonstrated that upregulation of HEF1 expression marks and induces metastasis, while high endogenous levels of p130Cas are associated with poor prognosis in breast cancer, emphasizing the clinical relevance of Cas proteins. Better understanding of the complete protein family should better inform prediction of cancer incidence and prognosis.

Address correspondence to: Erica A. Golemis (EA_Golemis{at}fccc.edu)






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