(D) SMAD3 gain-of-function increases BRAFi-resistance. Determination of BRAFi half maximal inhibitory concentrations (IC50 values) for 501Mel cell lines (Log[Vem] (nM)). Parental 501Mel cells (n=5), 501Mel cells expressing dCas9 and HSF1-p65-MS2 (named here 501Mel 2+, n=5), the 501Mel 2+ cells expressing a control guide (backbone, n=5) and the 501Mel 2+cells overexpressing SMAD3 (n=3 biologically independent experiments). A representative experiment has been chosen. Dotted line is used to determine the IC50 values. 