5-FU-induced HMGB1 release was blocked by TNF-α antibody in C3KO cells (Supplementary Figure S5H), supporting that TNF-α promotes cell killing after severe DNA damage.24 Interestingly, TCGA data indicated little or no RIP3 expression in a substantial fraction of colon cancers compared with normal tissues (N=304) (Supplementary Figure S6). Here, TNF is linked to malignant colon neoplasm.