TY - JOUR A1 - Wiegering, Armin A1 - Pfann, Christina A1 - Uthe, Friedrich Wilhelm A1 - Otto, Christoph A1 - Rycak, Lukas A1 - Mäder, Uwe A1 - Gasser, Martin A1 - Waaga-Gasser, Anna-Maria A1 - Eilers, Martin A1 - Germer, Christoph-Thomas T1 - CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression JF - PLoS ONE N2 - 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. KW - caco-2 cells KW - carcinomas KW - colon KW - colorectal cancer KW - MAPK signaling cascades KW - metastasis KW - protein expression KW - small interferring RNA Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97252 ER -