Furthermore, overexpression of malic enzyme 1 (ME1) drives metastasis through a dual pathway: 1) catalyzing malate decarboxylation to generate NADPH, maintaining a reductive microenvironment (89, 90); and 2) the activation of the ROS-ZEB1 signaling axis induces EMT and suggests its potential as a pan-cancer therapeutic target, as evidenced by an 80% decrease in HCC cell invasiveness following ME1 knockdown with shRNA (91). The gene discussed is ME1; the disease is hepatocellular carcinoma.