Signal Transduction Mechanisms of Focal Adhesions: Src and FAK-Mediated Cell Response

Cell-to-substrate adhesion sites, also known as focal adhesion sites (FAs), are complexes of different proteins on the cell surface. FAs play important roles in communication between cells and the extracellular matrix (ECM), leading to signal transduction involving different proteins that ultimately produce the cell response. This cell response involves cell adhesion, migration, motility, cell survival, and cell proliferation. The most important component of FAs are integrins. Integrins are transmembrane proteins that receive signals from the ECM and communicate them to the cytoplasm, thus activating several downstream proteins in a signaling cascade. Cellular Proto-oncogene tyrosine-protein kinase Src (c-Src) and focal adhesion kinase (FAK) are non-receptor tyrosine kinases that functionally interact to promote crucial roles in FAs. c-Src is a tyrosine kinase, activated by autophosphorylation and, in turn, activates another important protein, FAK. Activated FAK directly interacts with the cytoplasmic domain of integrin and activates other FA proteins by attaching to them. These proteins activated by FAK then activate other downstream pathways such as mitogen-activated protein kinase (MAPK) and Akt pathways involved in cell proliferation, migration, and cell survival. Src can induce detachment of FAK from the integrin to increase the focal adhesion turnover. As a result, the Src-FAK complex in FAs is critical for cell adhesion and survival mechanisms. Overexpression of FA proteins has been linked to a variety of pathological disorders, including cancers, growth retardation, and bone deformities. FAK and Src are overexpressed in various cancers. This review, which focuses on the roles of two important signaling proteins, c-Src and FAK, attempts to provide a thorough and up-to-date examination of the signal transduction mechanisms mediated by focal adhesions. The author also described that FAK and Src may serve as potential targets for future therapies against diseases associated with their overexpression, such as certain types of cancer.