We also provide evidence that Klotho expression confers hepatoma cells with resistance to anoikis via activating VEGFR2/PAK1 signaling, which could be reversed by inhibition with PAK1 allosteric inhibitor IPA3 or VEGFR2 inhibitor Axitinib administration in Klotho-overexpressed hepatoma cells. Here, KDR is linked to hepatocellular carcinoma.