A novel Cas family member, HEPL, regulates FAK and cell spreading.
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.
Singh
Mahendra K
MK
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Dadke
Disha
D
Nicolas
Emmanuelle
E
Serebriiskii
Ilya G
IG
Apostolou
Sinoula
S
Canutescu
Adrian
A
Egleston
Brian L
BL
Golemis
Erica A
EA
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003001:Cloning, Molecular; D050719:Crk-Associated Substrate Protein / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000502:physiology*; D022001:Focal Adhesions / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000503:physiopathology; D010802:Phylogeny; D011247:Pregnancy; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; C533047:CASS4 protein, human; D050719:Crk-Associated Substrate Protein; D012333:RNA, Messenger; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human