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Significance TAK1 deficiency has been shown to promote liver cancers; however, the mechanism is unclear. Here we show that TAK1 deficiency promotes RIPK1-mediated inflammation to promote cancer development. Our study highlights the role of RIPK1 as an important driver of inflammatory cytokine production in livers, which includes CCL2 and CCR2+ macrophage infiltration that are prominent in human pathology from liver pathology, and implications for additional human diseases, such as inflammatory bowel disease and Alzheimer’s disease.

Hepatocyte-specific TAK1 deficiency drives RIPK1 kinase-dependent inflammation to promote liver fibrosis and hepatocellular carcinoma