Focal adhesion kinase as a cancer therapy target

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that resides at the sites of focal adhesions. The 125 kDa FAK protein is encoded by the FAK gene located on human chromosome 8q24. Structurally, FAK consists of an amino-terminal regulatory FERM domain, a central catalytic kinase domain, and a carboxy-terminal focal adhesion targeting domain. FAK has been shown to be an important mediator of cell adhesion, growth, proliferation, survival, angiogenesis and migration, all of which are often disrupted in cancer cells. Normal tissues have low expression of FAK, while primary and metastatic tumors significantly overexpress this protein. This review summarizes expression of FAK by immunohistochemical staining in different tumor types and presents several FAK inhibition therapy approaches.

Fig. 1

Overexpression of Focal Ahhesion Kinase (FAK) in breast cancer tumors. Immunohistochemistry (IHC) staining was performed on breast (A) and colon (B) tumor (right) and matched normal (left) tissue samples. FAK 4.47 antibody (Upstate) was used for IHC.

Fig. 2

The structure of Focal Adhesion Kinase and its interacting proteins with intracellular signaling. FAK structure has N-terminal (including FERM domain); Central Kinase and C-terminal domains. The N-terminal domain has Y397 site, the main autophosphorylation site. The Kinase domain has Y576/Y577 tyrosines, critical for kinase activity of FAK. The C-terminal domain has main Y861 and Y925 tyrosines. FAK has many interacting binding partners and plays role in motility, invasion, metastasis, proliferation, adhesion, angiogenesis, lymphangiogenesis and survival.