Expression Of The P53 Target Cdip Correlates With Sensitivity To Tnf Alpha-Induced Apoptosis In Cancer Cells

TNF alpha is a pleiotropic cytokine that signals for both survival and apoptotic cell fates. It is still unclear that the dual role of TNF alpha can be regulated in cancer cells. We previously described an apoptotic pathway involving p53 -> CDIP -> TNF alpha 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 TNF alpha apoptotic cell fate, survival, or death. We show that CDIP mediates sensitivity to TNF alpha-induced apoptosis and that cancer cells with endogenous CDIP expression are inherently sensitive to the growth-suppressive effects of TNF alpha in vitro and in vivo. Thus, CDIP expression correlates with sensitivity of cancer cells with TNF alpha, and CDIP seems to be a regulator of the p53-mediated death versus survival response of cells to TNF alpha. This CDIP-mediated sensitivity to TNF alpha-induced apoptosis favors pro- over antiapoptotic program in cancer cells, and CDIP may serve as a predictive biomarker for such sensitivity. Cancer Res; 72(9); 2373-82. (C) 2012 AACR.