Tyciakova S, Valova V, Svitkova B, et al. - Researchers intended to explain the diverse cellular response to tumor necrosis factor alpha (TNFα), and this is why they engineered melanoma and colorectal carcinoma cell lines stably overexpressing this cytokine, in this study. They noted that the following two genes were significantly upregulated under the TNFα overexpression: proinflammatory cytokine IL6 (interleukin 6) gene in melanoma cells A375 and gene for pro-apoptotic ligand TRAIL (TNF-related apoptosis-inducing ligand) in colorectal carcinoma cells HT29, both mediated by TNFα/TNF receptor 1 signaling. On day 3, elevated autophagy was exhibited by malignant melanoma line A375, followed by premature senescence on day 6. Both processes appeared to be interlinked, following earlier apoptosis induction and deregulation of mitochondrial functions. Both melanoma and colorectal carcinoma cells displayed changed mitochondrial status, lowered adenosine triphosphate generation, lowered mitochondrial mass, and alterations in mitochondrial morphology (shortened and condensed mitochondria). Overall, in vitro analysis of direct TNFα impact revealed two distinct consequences in tumor cells of different origin, in non-epithelial malignant melanoma cells of neural crest origin, and in colorectal carcinoma cells derived from the epithelium.