title: Expression of the p53 target CDIP correlates with sensitivity to TNFα-induced apoptosis in cancer cells.
abstract: 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.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Brown-Endres
authors.forename: David
authors.initials: D
authors.lastname: Schoenfeld
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.forename: Hyung-Gu
authors.initials: HG
authors.lastname: Kim
authors.forename: Takushi
authors.initials: T
authors.lastname: Namba
authors.forename: César
authors.initials: C
authors.lastname: Muñoz-Fontela
authors.forename: Anna
authors.initials: A
authors.lastname: Mandinova
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Aaronson
authors.forename: Sam W
authors.initials: SW
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C522864:CDIP1 protein, human; C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C495901:TP53 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D048670:MAP Kinase Kinase 4