The IKKβ‐USP30‐ACLY Axis Controls Lipogenesis and Tumorigenesis

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death that develops as a consequence of obesity, cirrhosis, and chronic hepatitis. However, the pathways along which these changes occur remain incompletely understood. APPROACH AND RESULTS: -treated mice, USP30 deletion attenuated lipogenesis, inflammation, and tumorigenesis regardless of diet. The combination of ACLY inhibitor and programmed death ligand 1 antibody largely suppressed chemical-induced hepatocarcinogenesis. The IKKβ-USP30-ACLY axis was also found to be up-regulated in human HCCs. CONCLUSIONS: This study identifies an IKKβ-USP30-ACLY axis that plays an essential and wide-spread role in tumor metabolism and may be a potential therapeutic target in HCC.