Consistent with this, EGFR signaling counteracts the proapoptotic effects of TGF-β in normal hepatocytes and HCC cells, in a large part by blocking TGF-β-induced NOX4 upregulation and ROS accumulation via the clathrin- and PI3K/Akt-dependent pathway [204,205,206]. Here, TGFB1 is linked to hepatocellular carcinoma.