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Cancer Res DOI:10.1158/0008-5472.CAN-11-3369

Expression of the p53 target CDIP correlates with sensitivity to TNFα-induced apoptosis in cancer cells.

Publication TypeJournal Article
Year of Publication2012
AuthorsBrown-Endres, L, Schoenfeld, D, Tian, F, Kim, H-G, Namba, T, Muñoz-Fontela, C, Mandinova, A, Aaronson, SA, Lee, SW
JournalCancer Res
Date Published2012 May 01
KeywordsAnimals, Apoptosis, Apoptosis Regulatory Proteins, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, Interleukin-8, MAP Kinase Kinase 4, MAP Kinase Signaling System, Mice, Mice, Nude, NF-kappa B, Reactive Oxygen Species, Recombinant Proteins, Tumor Necrosis Factor-alpha, Tumor Suppressor Protein p53

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.


Alternate JournalCancer Res.
PubMed ID22549949
PubMed Central IDPMC3349239
Grant ListR01 CA085681-10 / CA / NCI NIH HHS / United States
R01 CA085681 / CA / NCI NIH HHS / United States
R01 CA142805-03 / CA / NCI NIH HHS / United States
R01 CA142805 / CA / NCI NIH HHS / United States
P01 CA080058 / CA / NCI NIH HHS / United States
P01 CA080058-13 / CA / NCI NIH HHS / United States
CA142805 / CA / NCI NIH HHS / United States
CA085681 / CA / NCI NIH HHS / United States
CA80058 / CA / NCI NIH HHS / United States
R01 CA078356 / CA / NCI NIH HHS / United States