Molecular cross-talk between the liver and white adipose tissue links excessive noURIshment to hepatocellular carcinoma

In their recent study published in Cancer Cell, Gomes and colleagues uncovered a novel mechanism driving obesity-triggered hepatocellular carcinoma (HCC). The authors revealed a feed-forward loop between hepatic unconventional prefoldin RPB5 interactor (URI) and cytokine interleukin-17A (IL-17A), and showed that chronically high expression of both proteins induces DNA damage, followed by systemic inflammation, which initiates non-alcoholic steatohepatitis (NASH) and HCC. URI and IL-17A are involved in cross-talk between the liver and white adipose tissue (WAT), with lipolysis, neutrophil infiltration and insulin resistance occurring in WAT, resulting in hepatosteatosis, injury and HCC in the liver. These results suggest that targeting URI and IL-17 levels may be a useful therapeutic strategy in the treatment of obesity-driven HCC.