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Abstract

Since its initial discovery as a substrate and binding partner for the Src oncogene, a role for the focal adhesion kinase (FAK) in cancer has been speculated. In this review the clinical evidence correlating FAK overexpression with cancer and the experimental evidence demonstrating that FAK can control some phenotypes associated with cancer will be discussed. In addition, the emerging theme of interactions between the FAK and growth factor signaling pathways will be described. The evidence presented in this review provides a compelling case for a role for FAK in the pathology of human cancer.

Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model

“…In analysing published gene array data that compared the mRNA profile of benign breast tissue versus breast carcinoma (Sorlie et al, 2001) and normal lung tissue versus lung adenocarcinoma (Bhattacharjee et al, 2001), both FAK and uPA expressions are significantly upregulated in the carcinoma samples. As FAK expression is elevated in a variety of tumor cells and malignant tissues (Gabarra-Niecko et al, 2003), and FAK re-expression in v-Src-transformed FAKÀ/À fibroblasts promotes uPA expression (S Mitra, unpublished results), our findings support the conclusion that enhanced FAK signaling promotes uPA expression in a variety of cell types and that this signaling linkage contributes to tumor progression.…”

“…In normal cells, FAK functions as an important regulator of cell motility, proliferation and anchorage-dependent cell survival (Hanks et al, 2003;. In many tumor cells and malignant tissue, FAK expression is elevated (Gabarra-Niecko et al, 2003) and the role of FAK in promoting tumor progression remains an area of active investigation (McLean et al, 2005).…”

Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK

“…Moreover, FAK expression has been shown to associate with tumor invasiveness (Owens et al, 1995;Gabarra-Niecko et al, 2003), and increased FAK expression/activity is frequently correlated with highly malignant or metastatic tumors having a poor prognosis (McLean et al, 2005). Our data indicate that stable overexpression of FAK in MM cells increases their invasiveness, and that re-expression of merlin can markedly suppress FAK-related invasiveness.…”

Cellular Characterization of a Novel Focal Adhesion Kinase Inhibitor

“…The FAK 4 family kinases (which include FAK and Pyk2) regulate cell adhesion, migration, and proliferation in a variety of cell types (for review see Refs. [1][2][3].…”

“…The importance of FAK as a regulator of normal cellular function is underscored by the number of cancers reported to have alterations in FAK expression and/or activity, including colon, breast, thyroid, prostate, cervical, ovarian, head and neck, oral, liver, stomach, sarcoma, glioblastoma, and melanoma (4,5). Additionally, alterations in FAK expression and/or activity have been associated with tumorigenesis and increased metastatic potential (4,5).…”