A375 cells expressing STAG2 shRNA showed lower sensitivity to BRAFi dabrafenib compared to scrambled control shRNA in MTS-based cell viability assays (Fig. 2a). Knockdown of STAG2 also resulted in increases of basal pERK levels and reduction of the ability of dabrafenib to inhibit ERK phosphorylation in these cells (Fig. 2b). However, phospho-Akt and phospho-S6 levels were not affected by knockdown of STAG2 (Fig. 2b). Similarly, inducible expression of an independent shRNA against STAG2 also decreased the sensitivity to either dabrafenib or vemurafenib BRAFi in SKMEL28, A375 and M14 cells (Fig. 2c,d, Supplementary Fig. 2a–h). Knockdown of STAG2 also decreased the sensitivities to MEKi trametinib alone and in combination with dabrafenib in A375 cells.