Moreover, stable overexpression of Skp2 S256A, but not Skp2 S256D, in H1975 cells heightened the response of H1975 cells to Gefitinib (Fig. 6g and Supplementary Fig. 8g), suggesting that AMPK-mediated Skp2 S256 phosphorylation may cause the resistance of H1975 cells to Gefitinib, and targeting AMPK, Skp2, or AMPK-mediated Skp2 S256 phosphorylation may overcome the resistance of NSCLC cells to Gefitinib. This evidence concerns the gene PRKAA1 and non-small cell lung carcinoma.