Targeting of eIF6-driven translation induces a metabolic rewiring that reduces NAFLD and the consequent evolution to hepatocellular carcinoma

At IRBM we are passionate about helping companies develop medicines in a wide range of diseases and our scientists support the fundamental understanding of disease mechanisms. Science is about collaboration, and publication is an integral part of the scientific process. So, we are delighted to have out latest scientific paper published, produced in collaboration with several institutions including the University of Milan, and Milan’s Istituto Nazionale di Genetica Molecolare (INGM). The paper in Nature Communications looked at whether a specific element of hepatocellular (liver) cancer progression can be reduced (depleted) by decreasing eukaryotic Initiation Factor 6 (eIF6) activity in the liver. The accumulation of lipids in the liver is known as nonalcoholic fatty liver disease (NAFLD). The potential evolution of NAFLD to cirrhosis and hepatocellular carcinoma (HCC) makes NAFLD of clinical importance. We provide proof-of-concept that in vitro pharmacological inhibition of eIF6 activity recapitulates the protective effects of eIF6 depletion. This suggests the existence of a targetable, evolutionarily conserved translation circuit optimized for lipid accumulation and tumor progression. The development of specific eIF6 inhibitors to help regulate lipid metabolism could provide a therapeutic target in the NAFLD-HCC progression.