Fig. 6
Hepatic activation of FOXO3 induces oxidative damage and protection system, and FOXO3 supports hepatocellular carcinogenesis in diverse ways. a Expression of Gpx1, Gpx2, and Gpx3 by qPCR in livers from 9-week-old control and FOXO3CAHep transgenic mice (n = 4). b Higher NADPH/NADP+ ratio in 9-week-old FOXO3CAHep versus control mice. c Expression of G6pdx by qPCR in livers from 9-week-old control and FOXO3CAHep transgenic mice. d Graphical abstract. Here we propose that hepatic FOXO3 activates and balances both ROS-promoting and ROS-protecting pathways. On one side, hepatic activation of FOXO3 leads to oxidative damage and Akt activation, but on the other side, high expression of G6PD and NADPH, as well as glutathione peroxidases acting against oxidative damage. This balanced ROS control system presumably makes hepatocytes resistant against cellular death and crisis. The whole system can cooperatively support hepatocellular carcinogenesis