FAK downregulation suppresses stem-like properties and migration of human colorectal cancer cells.

Abstract

Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase, which is overexpressed in colorectal cancer cells. FAK could be activated by phosphorylation to participate in the transduction of multiple signaling pathways and self-renewal of cancer stem cells. Whether the downregulation of FAK inhibits the metastasis in colorectal cancer through the weakening of stem cell-like properties and its mechanisms has yet to be established. CD44, CD133, c-Myc, Nanog, and OCT4 were known to mark colorectal cancer stem cell properties. In this study, AKT inhibitor (MK-2206 2HCl) or FAK inhibitor (PF-562271) decreased the expression of stem cell markers (Nanog, OCT4, CD133, CD44, c-Myc) and spheroid formation in colorectal cancer. Moreover, FAK and AKT protein was shown to interact verified by co-immunoprecipitation. Furthermore, downregulation of FAK, transfected Lenti-FAK-EGFP-miR to colorectal cancer cells, reduced p-AKT but not AKT and decreased the expression of stem cell markers and spheroid formation in colorectal cancer. In conclusion, we demonstrated that downregulation of FAK inhibited stem cell-like properties and migration of colorectal cancer cells partly due to altered modulation of AKT phosphorylation by FAK.