Emerging Roles of Focal Adhesion Kinase in Cancer

Figure 1

Model for FAK signal transduction in cancer cells and tumor microenvironment. The activation of FAK principally initiated by integrin engaged with ECMs and also by growth factor receptors enables regulating cell survival, proliferation, migration, invasion, and metastasis in relation to cancer development. Subsequently, the autophosphorylated (on Tyr397) FAK/Src complex empowers tyrosine phosphorylation cascades in modulating versatile signal pathways. For example, FAK modulates endophilin A2 phosphorylation by Src or PI3K-AKT signaling in cancer stem cells. In endothelial cells, vascular endothelial growth factor-A (VEGF-A)/VEGF or angiopoietin-1 signalling regulates FAK-mediated PI3K/AKT activation to promote migration, sprouting, and angiogenesis. FAK also regulates the expression of growth factors or cytokines in tumor-associated macrophages to facilitate cancer progression. In response to LOXL2 stimulation, FAK affects the α-SMA expression and AKT signaling to control invasion, antiapoptosis, and proliferation in cancer-associated fibroblasts.