Roles for Crk in Cancer Metastasis and Invasion

The Crk family of adaptors is implicated in regulating various biological and pathological processes such as cell proliferation, adhesion, migration, invasion, phagocytosis, and survival. A large number of studies have shown that Crk plays an important role in aggressive and malignant behaviors of human cancers. In immunohistochemical analyses and gene-expression profiles, enhanced expression of Crk has been identified in adenocarcinomas of lung, breast, and stomach and in sarcomas and glioma. Overexpression of Crk in tumor cells induces the prominent tyrosine phosphorylations of scaffolding molecules such as p130(Cas) and paxillin through Src family tyrosine kinases and stimulates the activation loop of intracellular signalling, ultimately contributing to the increased motility and aggressive potential of cancer cells. Crk proteins thus are not simply conduits for intracellular signal transduction but also can control the amplitude of signalling. This review summarizes the significance of Crk and its mediated signaling assemblies, particularly in regulating tumor metastasis and invasion, and discusses the possibilities that they are potential cancer therapeutic targets.