CAS Proteins in Normal and Pathological Cell Growth Control

Cell Mol Life Sci. 2010 Apr;67(7):1025-48. doi: 10.1007/s00018-009-0213-1. Epub 2009 Nov 25.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adaptor Proteins, Signal Transducing / physiology
  • Apoptosis
  • Cell Movement
  • Crk-Associated Substrate Protein / chemistry
  • Crk-Associated Substrate Protein / metabolism*
  • Crk-Associated Substrate Protein / physiology
  • Humans
  • Neoplasms / metabolism
  • Phosphoproteins / metabolism
  • Phosphoproteins / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • BCAR1 protein, human
  • Crk-Associated Substrate Protein
  • NEDD9 protein, human
  • Phosphoproteins