Furthermore, our data indicate that UBE2S upregulation in HCC is induced by transcription factor FOXM1, and UBE2S renders PTEN ubiquitinated at Lys60 and Lys327, phosphorylating AKT to enhance HCC cell chemoresistance, which is attenuated by allosteric AKT inhibitor, MK2206. This evidence concerns the gene AKT1 and hepatocellular carcinoma.