In conclusion, in this study we demonstrated that SHP-1 dephosphorylates PKM2Y105 to inhibit the Warburg effect and nucleus-dependent cell proliferation, and the dephosphorylation of PKM2Y105 by SHP-1 determines the efficacy of targeted drugs for HCC treatment (Figure 6B). The gene discussed is PTPN6; the disease is hepatocellular carcinoma.