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CAS proteins in normal and pathological cell growth control

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Abstract

Proteins of the CAS (Crk-associated substrate) family (BCAR1/p130Cas, NEDD9/HEF1/Cas-L, EFS/SIN and CASS4/HEPL) are integral players in normal and pathological cell biology. CAS proteins act as scaffolds to regulate protein complexes controlling migration and chemotaxis, apoptosis, cell cycle, and differentiation, and have more recently been linked to a role in progenitor cell function. Reflecting these complex functions, over-expression of CAS proteins has now been strongly linked to poor prognosis and increased metastasis in cancer, as well as resistance to first-line chemotherapeutics in multiple tumor types including breast and lung cancers, glioblastoma, and melanoma. Further, CAS proteins have also been linked to additional pathological conditions including inflammatory disorders, Alzheimer’s and Parkinson’s disease, as well as developmental defects. This review will explore the roles of the CAS proteins in normal and pathological states in the context of the many mechanistic insights into CAS protein function that have emerged in the past decade.

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Acknowledgments

We are grateful to Dr. Mark Andrake of the Fox Chase Cancer Center Molecular Modeling Facility for help in producing Fig. 1a. N.T. and E.A.G. were supported by NIH R01 CA63366 and R01 CA113342, and by Pennsylvania Tobacco Settlement funding (to E.A.G.); J.L.L. was supported by NIH T32 CA009035; and all authors by NIH core grant CA06927 and a gift from the Pew Charitable Trust (to Fox Chase Cancer Center).

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Correspondence to Erica A. Golemis.

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N. Tikhmyanova and J. L. Little have contributed equally.

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Tikhmyanova, N., Little, J.L. & Golemis, E.A. CAS proteins in normal and pathological cell growth control. Cell. Mol. Life Sci. 67, 1025–1048 (2010). https://doi.org/10.1007/s00018-009-0213-1

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