HK2 and hepatocellular carcinoma: Metformin together with hexokinase 2 (HK2) depletion synergistically interferes with mTORC1 activation through the induction of the mTORC1 inhibitor REDD1 (regulated in development and DNA damage) in hepatocellular carcinoma cells, even upon depletion of AMPKα1 and AMPKα2 (52).