FAK signaling in neoplastic disorders: a linkage between inflammation and cancer.
Focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, is frequently overexpressed in various tumors and its expression shows good correlation with the progression of tumor. FAK is involved in a diverse range of critical cellular events including spreading, proliferation, migration, and invasion. In addition to these cellular functions, we found that FAK signaling played a critical role in the production of matrix metalloproteinases (MMP) such as MMP-2 and MMP-9 and subsequently activated tumor invasion. Moreover, we found that tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine that acts as an endogenous tumor promoter, activated FAK signaling and enhanced tumor invasion. Since the tumor microenvironment that is largely orchestrated by cytokines is a critical component of tumor progression, these results suggest the importance of FAK as a signaling molecule involved in tumorigenesis. Here, we review the general structure and binding partners of FAK, its regulatory mechanism, and expression in tumors. By summarizing our recent studies, we focus on the critical role of FAK that links cancer with inflammation.
Mon
Naing Naing
NN
Division of Cancer Biology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa ku, Nagoya 466, Japan. mhamagu@med.nagoya-u.ac.jp
Ito
Satoko
S
Senga
Takeshi
T
Hamaguchi
Michinari
M
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D020782:Matrix Metalloproteinases / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020782:Matrix Metalloproteinases