FAK Signaling in the Acquisition of a Cancerous Phenotype in Breast Epithelial Cells
Abstract
As a substrate and binding partner for the Src oncogene, a role for the focal adhesion kinase (FAK) in cancer has been speculated. FAK mediates cellular processes including cell motility, survival, and proliferation. Thus, aberrant FAK signaling could lead to pathological effects, including oncogenesis. FAK is overexpressed in a variety of tumors. We have established a cancer cell model system to study the role of aberrant FAK signaling in human cancer. Increased FAK signaling was achieved with the expression of a constitutive activated mutant of FAK, SuperFAK. In contrast, FAK signaling was inhibited using FRNK, a FAK dominant negative. The effect of altered FAK signaling in the acquisition or loss of transformation phenotypes in normal and cancer breast epithelial cells was monitored. Decreased FAK signaling by FAK led to a loss in adhesion independent growth of the breast cancer cells. FRNK had no effect on the proliferation nor the survival of the cells. Elevation of FAK signals by overexpression of the hyperactive FAK mutant increased the tumorigenic capacity of the breast cancer epithelial cells. These data demonstrate the role for aberrant FAK signaling as a cause of some of the phenotypic changes that occur when a cell becomes oncogenically transformed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA416677
Entities
People
- Michael D. Schaller
- Veronica Gabarra-niecko
Organizations
- University of North Carolina at Chapel Hill