In HT-29 colon cancer cells undergoing TNFα-induced necroptosis in the presence of the second mitochondria-derived activator of caspases mimetics and the caspase-8 inhibitor zVAD, TNF stimulation triggers a biphasic NF-κB activation, characterized by sustained nuclear accumulation of p65 that promotes proinflammatory cytokine transcription. Here, CASP8 is linked to colonic neoplasm.