Cancer Research · 2012 · 11 citations · 16 references
Life SciencesCancer BiologyOncologyApoptosisCell SignalingSignal TransductionApoptosis In CancerApoptosis RegulationApoptosis ResistanceApoptotic Signal TransductionApoptotic SignalingInflammatory SignalingApoptotic Signaling In CancerApoptotic Signaling PathwaysJnk Pathway ActivationJnk Signaling PathwayP53-mediated ApoptosisP53-mediated Cell DeathPredictive Biomarker DevelopmentTumor Necrosis Factor-mediated Apoptosis
TNFα is a pleiotropic cytokine that signals for both survival and apoptotic cell fates. It is still unclear that the dual role of TNFα can be regulated in cancer cells. We previously described an apoptotic pathway involving p53→CDIP→TNFα 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 TNFα apoptotic cell fate, survival, or death. We show that CDIP mediates sensitivity to TNFα-induced apoptosis and that cancer cells with endogenous CDIP expression are inherently sensitive to the growth-suppressive effects of TNFα in vitro and in vivo. Thus, CDIP expression correlates with sensitivity of cancer cells with TNFα, and CDIP seems to be a regulator of the p53-mediated death versus survival response of cells to TNFα. This CDIP-mediated sensitivity to TNFα-induced apoptosis favors pro- over antiapoptotic program in cancer cells, and CDIP may serve as a predictive biomarker for such sensitivity.
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