Furthermore, in the present study, the compensation experiments disclosed that activating AKT or overexpression of CTNNB1 promoted stemness, reduced sorafenib sensitivity, and further attenuated the effect of SENP2 overexpression on stemness and sorafenib sensitivity in HCC cells, indicating that the AKT/GSK3β/CTNNB1 signaling pathway was essential for the regulation of SENP2 in stemness and sensitivity to sorafenib in HCC cell lines. This evidence concerns the gene AKT1 and hepatocellular carcinoma.