FAK/PYK2 promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3β

• DOI: 10.7554/elife.10072
• Publication Date: 2015-08-14T11:39:26Z
• Authors: Chenxi Gao; Guangming Chen; Shih-Fan Kuan; Dennis Han Zhang; David D Schlaepfer; Jing Hu
• Keywords: Beta-catenin

Aberrant activation of Wnt/β-catenin signaling plays an unequivocal role in colorectal cancer, but identification effective Wnt inhibitors for use cancer remains a tremendous challenge. New insights into the regulation this pathway could reveal new therapeutic point intervention, therefore are greatly needed. Here we report novel FAK/PYK2/GSK3βY216/β-catenin axis: FAK and PYK2, elevated adenomas APCmin/+ mice human tissues, functioned redundantly to promote by phosphorylating GSK3βY216 reinforce output—β-catenin accumulation intestinal tumorigenesis. We previously showed that Wnt-induced β-catenin requires GSK3β/β-TrCP interaction; current study revealed phosphorylation was molecular determinant GSK3β recruitment β-TrCP. Pharmacological inhibition FAK/PYK2 suppressed adenoma formation accompanied with reduced levels phospho-GSK3βY216 β-catenin, indicating FAK/PYK2/GSK3βY216 axis is critical APC driven