Stimulation of protein kinase C‐α suppresses colon cancer cell proliferation by down‐regulation of β‐catenin

Abstract

Abstract We reported previously that protein kinase C‐α (PKC‐α) negatively regulates Wnt/β‐catenin signalling pathway. The current study explores the role of PKC‐α in the regulation of proliferation of colon cancer cells, which contain aberrant up‐regulation of intracellular β‐catenin. In colon tissue and cells, an inverse correlation was observed between the expression levels of PKC‐α and intracellular β‐catenin. Activation of PKC‐α inhibited β‐catenin response transcription by down‐regulation of intracellular β‐catenin and induced phosphorylation of the N‐terminal serine and threonine residues (Ser33/Ser37/Thr41) of β‐catenin, marking it for proteasomal degradation, in colon cancer cells. Pharmacological inhibition or depletion of PKC‐α‐abrogated PKC‐α‐mediated β‐catenin down‐regulation and phosphorylation in colon cancer cells. Notably, the Ser45 residue of β‐catenin was essential for PKC‐α‐induced β‐catenin down‐regulation in colon cancer cells. Moreover, PKC‐α activation repressed the expression of cyclin D1 and c‐myc , which are known β‐catenin target genes, and thus inhibited the growth of colon cancer cells. These findings suggest that PKC‐α negatively regulates colon cancer cell proliferation via β‐catenin phosphorylation/down‐regulation and may facilitate the development of new strategies to treatment of colon cancer.