Stimulation of protein kinase C-alpha suppresses colon cancer cell proliferation by down-regulation of beta-catenin

J Cell Mol Med. 2009 Aug;13(8B):2171-80. doi: 10.1111/j.1582-4934.2009.00683.x.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Proliferation*
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology
  • DNA Primers
  • Down-Regulation*
  • Enzyme Activation
  • Humans
  • Immunohistochemistry
  • Protein Kinase C-alpha / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • beta Catenin / metabolism*


  • DNA Primers
  • beta Catenin
  • Protein Kinase C-alpha