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The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether  CIP2A  expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed  CIP2A  mRNA expression by real-time PCR in 104 colon cancer samples.  CIP2A  mRNA was overexpressed in colon cancer samples and  CIP2A  expression levels correlated significantly with tumour stage. We found that  CIP2A  serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.

CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression