1. JNK, FAK, Src, and BET inhibitors overcome the NGFRHigh drug‐resistant state in additional BRAFV600E/D melanoma lines
JNK, FAK, Src, and BET inhibitors overcome the NGFRHigh drug‐resistant state in additional BRAFV600E/D melanoma lines ANGFR protein levels measured in duplicate by immunofluorescence in seven BRAFV600E/D cell lines treated with vemurafenib at indicated doses for 48 h.BCorrelation between vemurafenib‐induced changes in c‐Jun and NGFR protein levels across nine BRAFV600E/D melanoma cell lines. Cells were treated with five doses of vemurafenib (0, 0.1, 0.32, 1, and 3.2 μM) for 48 h. c‐Jun and NGFR protein levels measured by immunofluorescence at each condition were averaged across two replicates and normalized to DMSO‐treated controls. The area under the dose–response curve (AUC) for the two measurements (c‐Jun and NGFR) was calculated, z‐score‐scaled across nine cell lines, and their pairwise Pearson's correlation was reported.C, DRelative viability of A375 and WM115 cells treated in 3 replicates for 72 h with vemurafenib or vemurafenib plus trametinib (10:1 dose ratio) in combination with indicated kinase inhibitors (C) or BET inhibitors (D).E, FPairwise comparison between NGFR and Ki‐67 levels in A375 and WM115 cells treated with vemurafenib in combination with indicated kinase inhibitors (E) or BET inhibitors (F). Drug doses, time points, and data normalization are similar to Figs 7C and 8C.Data information: Data in (A, C, D) are presented as mean ± SD.
Mohammad Fallahi‐Sichani et al. Mol Syst Biol 2017;13:905
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