Fig. 8

Ischemia reperfusion injury promotes recurrence of hepatocellular carcinoma in NAFLD via ALOX12–12HETE-GPR31 signaling axis. ALOX12–12-HETE pathway was activated during liver IRI and enhanced in NAFLD, which induced more severe HCC recurrence in fatty liver than normal. 12-HETE induced GPR31 dependent activation of EMT and MMPs via PI3K/AKT/NF-κB to enhance invasion ability of circulation tumor cells, which promoted more severe HCC recurrence in NAFLD