Focal adhesion kinase and its potential involvement in tumor invasion and metastasis.

Integrins are cell surface receptors which, in part, mediate the adhesion of cells to the extracellular matrix. In addition to providing a molecular "glue" essential for tissue organization and survival, integrins are dynamic signaling molecules. Integrins allow normal, nontransformed cells to sense that they are adhered to the extracellular matrix, thus providing a cell survival signal. This signal allows cells to proliferate in the presence of growth factors and in some instances prevents apoptosis. Integrins also mediate cell migration as it occurs in normal processes such as angiogenesis, wound healing, immune system function, and development. Aberrances in the expression and function of integrins contribute to many disease states including cancer. Focal adhesion kinase (FAK) becomes phosphorylated and activated during integrin-mediated cell adhesion. Focal adhesion kinase is a signal transducer of integrins (and certain soluble growth factors). Cells derived from FAK -/- mouse embryos exhibit reduced migration relative to wild-type cells. Cells which overexpress FAK show increased migration relative to wild-type cells. Focal adhesion kinase promotes cell survival under certain in vitro conditions. Focal adhesion kinase is overexpressed in invasive and metastatic colon, breast, thyroid, and prostate cancers. Enhanced FAK immunostaining is detected in small populations of preinvasive (carcinoma in situ) oral cancers and in large populations of cells in invasive oral cancers. Focal adhesion kinase is probably not a classical oncogene but may be involved in the progression of cancer to invasion and metastasis. It is hypothesized that overexpression of FAK in subpopulations of tumor cells leads to populations of cells with a high propensity toward invasion and metastasis. Focal adhesion kinase would have a dual role in this regard: Overexpression of FAK leads to (1) increased cell migration and (2) increased cell survival under anchorage-independent conditions. Further work is needed to test this model and to determine whether FAK represents a viable target for anticancer therapy.