Focal adhesion kinase and cancer.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that resides at the sites of integrin clustering, known as focal adhesions. The FAK protein has a molecular mass of 125kDa and 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, two proline-rich motifs, and a carboxy-terminal focal adhesion targeting domain. FAK has been shown to be an important mediator of cell growth, cell proliferation, cell survival and cell migration, all of which are often dysfunctional in cancer cells. Our lab was the first to isolate FAK from primary human tissue and link it to the process of tumorigenesis. We analyzed FAK mRNA expression in normal, invasive and metastatic human tissues and demonstrated through Northern blot analysis that normal tissues had very low levels of FAK mRNA while primary and metastatic tumors significantly overexpressed FAK. We also demonstrated and confirmed FAK overexpression in colorectal carcinoma and liver metastases with real-time PCR. In this review we summarized immunohistochemical data of FAK expression and role in different cancer types tumors and discussed FAK inhibition therapy approaches.
Golubovskaya
Vita M
VM
Department of Surgery, School of Medicine, University of Florida, Gainesville, FL, USA.
Kweh
Frederick A
FA
Cance
William G
WG
D002471:Cell Transformation, Neoplastic; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D004791:Enzyme Inhibitors; D051416:Focal Adhesion Protein-Tyrosine Kinases