SOX2 and melanoma: Importantly, the phosphomimetic mutant SOX2-S251E showed increased number of secondary spheres compared to SOX2-WT in basal condition and was able to prevent further increase in self-renewal ability following PLX4032 treatment (Fig. S9, C and D), suggesting that phosphorylation-dependent SOX2 hyperactivation is required to maintain a stem-like phenotype that could mitigate the response of melanoma cells to BRAFi.