Induced Apoptosis in Cancer Cells α TNF Expression of the p 53 Target CDIP Correlates with Sensitivity to Updated

TNFa is a pleiotropic cytokine that signals for both survival and apoptotic cell fates. It is still unclear that the dual role of TNFa can be regulated in cancer cells. We previously described an apoptotic pathway involving p53!CDIP!TNFa that was activated in response to genotoxic stress. This pathway operated in the presence of JNK activation; therefore, we postulated that CDIP itself could sensitize cells to a TNFa apoptotic cell fate, survival, or death. We show that CDIPmediates sensitivity to TNFa-induced apoptosis and that cancer cells with endogenous CDIP expression are inherently sensitive to the growth-suppressive effects of TNFa in vitro and in vivo. Thus, CDIP expression correlateswith sensitivity of cancer cells with TNFa, andCDIP seems to be a regulator of the p53-mediated death versus survival response of cells to TNFa. This CDIP-mediated sensitivity to TNFainduced apoptosis favors proover antiapoptotic program in cancer cells, and CDIP may serve as a predictive biomarker for such sensitivity. Cancer Res; 72(9); 2373–82. 2012 AACR.