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Originally published as MBC in Press, 10.1091/mbc.E07-09-0953 on February 6, 2008

Vol. 19, Issue 4, 1627-1636, April 2008

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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

Submitted September 21, 2007; Revised January 17, 2008; Accepted January 30, 2008
Monitoring Editor: Mark Ginsberg

For over a decade, p130Cas/BCAR1, HEF1/NEDD9/Cas-L, and Efs/Sin have defined the Cas (Crk-associated substrate) 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 are 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, whereas 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 help inform prediction of cancer incidence and prognosis.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-09-0953) on February 6, 2008.

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






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