American Association for Cancer Research
00085472can113369-sup-can_11-3369_meth_t1_f1-6_1687k.pdf (1.65 MB)

Supplementary Methods, Table 1, Figures 1-6 from Expression of the p53 Target CDIP Correlates with Sensitivity to TNFα-Induced Apoptosis in Cancer Cells

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journal contribution
posted on 2023-03-30, 21:26 authored by Lauren Brown-Endres, David Schoenfeld, Fang Tian, Hyung-Gu Kim, Takushi Namba, César Muñoz-Fontela, Anna Mandinova, Stuart A. Aaronson, Sam W. Lee

PDF file - 1.6MB, Table 1. Primers used for real-time PCR analysis of NF-kB target gene expression. Fig. S1. Recombinant human TNF�� rescues CDIP apoptosis in TNF�� knockdown cells. Fig. S2. TNF�� signaling was assessed in U2OS-CDIP cells 20 and 30 hours post-CDIP induction (dox), and 20 hours after treatment with 5 ng/mL recombinant human TNF�� (rhTNF��, boxed panel). Fig. S3. MAPK inhibitors do not block cell death induced by CDIP expression. Fig. S4. The NF-���� transcriptional program is altered in CDIP expressing cells. Fig. S5. The effects of IL-8 and ROS inhibition on CDIP��TNF�� apoptosis. Fig. S6. CDIP do not induce Fas.



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. Cancer Res; 72(9); 2373–82. ©2012 AACR.