Work

The combination of TPL2 knockdown and TNFα causes synthetic lethality via caspase-8 activation in human carcinoma cell lines

Year: 2019

Type: article

Abstract: Significance Tumor necrosis factor α (TNFα) fails to induce apoptosis in most tumor cells. Defining the mechanism(s) responsible for the protection of these cells from TNFα-induced apoptosis may have significant therapeutic implications. Here, we show that tumor progression locus-2 (TPL2), a MAP3 kinase activated by TNFα, protects from TNFα-induced apoptosis by preventing the activation of caspase-8, and that the combination of TPL2 knockdown and TNFα treatment induces synthetic lethality. More important, sensitivity to synthetic lethality can be predicted from the gene expression profiles of the tumor cells. In addition to their therapeutic potential, these results identify an important node in TNFα signaling.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1901465116