p38 MAPK-Dependent Phosphorylation of Transcription Factor SOX2 Promotes an Adaptive Response to BRAF Inhibitors in Melanoma Cells

Using functional studies, the authors demonstrated that SOX2 depletion increased sensitivity of melanoma cells to BRAF kinase inhibitors (BRAFi), whereas overexpression of a phosphomimetic SOX2-S251E mutant was sufficient to drive resistance and desensitize melanoma cells to BRAFi in vitro and in a Zebrafish xenograft model.