The role of focal adhesion kinase in tumor initiation and progression.
Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that acts as a primary regulator of focal adhesion signaling to regulate cell proliferation, survival and migration. While FAK is known to directly influence many fundamental adhesion and growth factor signaling pathways important in cancer and FAK is overexpressed in multiple human cancers studies addressing a causal role for FAK in tumor initiation and progression using transgenic models of human cancer had not been performed. Recently, using tissue-specific FAK-knockout in mouse models of human cancer, the consequences of FAK ablation in carcinoma were demonstrated by multiple independent research groups. Strong consensus evidence indicates that epithelial cells are able to transform in the absence of FAK, but do not undergo a malignant conversion to invasive carcinoma, and as such, metastasis is impaired. This is likely the consequence of decreased Src and p130Cas activation in concert with misregulated actin cytoskeleton dynamics and Rho GTPase signaling. Hence, FAK, as well as the FAK-regulating/regulated signaling network, are viable candidates for cancer metastasis therapies.
Provenzano
Paolo P
PP
Laboratory of Molecular Biology and Departments of Pharmacology and Biomedical Engineering, University of Wisconsin, Madison, WI, USA. ppproven@fhcrc.org
Keely
Patricia J
PJ
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018450:Disease Progression; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*
D051416:Focal Adhesion Protein-Tyrosine Kinases
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