Emerging Roles of Focal Adhesion Kinase in Cancer

Abstract

Focal adhesion kinase (FAK) is a cytoplasmic nonreceptor tyrosine kinase that enables activation by growth factor receptors or integrins in various types of human cancers. The kinase-dependent and kinase-independent scaffolding functions of FAK modulate the authentic signaling and fundamental functions not only in cancer cells but also in tumor microenvironment to facilitate cancer progression and metastasis. The overexpression and activation of FAK are usually investigated in primary or metastatic cancers and correlated with the poor clinical outcome, highlighting FAK as a potential prognostic marker and anticancer target. Small molecule inhibitors targeting FAK kinase activity or FAK-scaffolding functions impair cancer development in preclinical or clinical trials. In this review, we give an overview for FAK signaling in cancer cells as well as tumor microenvironment that provides new strategies for the invention of cancer development and malignancy.

Sushi repeat-containing protein X-linked 2 promotes angiogenesis through the urokinase-type plasminogen activator receptor dependent integrin αvβ3/focal adhesion kinase pathways

“…In tube-formation assays, the number of tube-like structures of HUVECs in the SRPX2 group was significantly increased compared to control group (p < 0.001), while pretreatment with the integrin αvβ3-neutralizing antibody significantly inhibited this effect (p < 0.001, Figure 3a), confirming integrin αvβ3 is a crucial mediator for the SRPX2/uPAR complex. In addition, FAK is a cytoplasmic tyrosine kinase that plays a critical role in integrin-mediated signal transductions as well as in angiogenesis and tumor progression (17,18). Tanaka et al (7) reported that SRPX2 increases FAK phosphorylation levels in several gastric cancer cells.…”

LEFTY2 Controls Migration of Human Endometrial Cancer Cells via Focal Adhesion Kinase Activity (FAK) and miRNA-200a

“…FAK is a component of focal adhesions considered as a point of convergence of integrin and growth factor mechanical signaling [39,49]. FAK is important for maintaining cell rigidity (stiffness) through promoting a static and highly aligned contractile cytoskeleton [50,51].…”

“…In FAK-deficient cells, reduced cytoskeletal stability is attributed to a compensatory increase of rhoA-kinase and ROCK activity [38,60,63]. Further, FAK directly interacts with multiple cell surface receptors and signaling proteins [39,60,62,64] thus mediating a variety of physiological responses. Therefore, by regulating the activity of FAK, LEFTY2 could contribute to regulation of other physiological processes beyond regulating actin polymerization and cell stiffness [65].…”

Matrix metalloproteinases in head and neck cancer: current perspectives

“…94 Collagen cross-linking induces tumor progression by activating FAK, PI3K, and Akt. 95 MMP1 induces epidermal hyperplasia and increases the susceptibility to tumorigenesis, invasion, and angiogenesis. 49 Since MMP3 is expressed by fibroblasts and tumor cells, it regulates cancer stem cells during tumor initiation and metastasis.…”