Yang et al. showed that pre-S deleted proteins could upregulate the expression and secretion of vascular endothelial growth factor (VEGF)-A, which could, in turn, bind to VEGF receptor-2 (VEGFR-2) in an autocrine or paracrine manner to activate the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR) signaling pathway in human hepatoma cell lines, in transgenic mouse livers, and in GGHs in HCC patients, which promoted cell proliferation [40]. The gene discussed is AKT1; the disease is hepatocellular carcinoma.