SGK activity is critical for the proliferation of thyroid cancer cells carrying PI3K activating mutations. A, heat map illustrating the effect of inhibitors of different PI3K-dependent AGC kinases on the proliferation of mouse and human thyroid cancer cell lines. Colored horizontal bars below the heat map indicate the known driver mutation for each cell line. B, Western blot analysis of the phosphorylation of the SGK target, NDRG1, in the thyroids from mice of the indicated genotypes. C, Effect of a reduced concentration (3µM) of the SGK inhibitor GSK650394 on the proliferation of mouse and human thyroid cancer cell lines. D, Correlation between the responses of representative thyroid cancer cell lines to low concentrations of the SGK inhibitors GSK650394 and EMD638683. E-F, Differential response to two different SGK inhibitors of mouse thyroid cancer cell lines proficient or impaired in AGC kinase activation. G, Western blot analysis of the phosphorylation of the SGK1 target, NDRG1, in the T4888M cells upon 6 hours treatment with the indicated inhibitors. H, Analysis of the proliferation of different PI3K-active thyroid cancer cell lines treated with the SGK inhibitor GSK650394.