fig6

Figure 6. Upregulated and downregulated proteins of WM164 and HT144 cells in the persister and drug-resistant state. (A) Volcano plots of significantly downregulated (blue) and upregulated (red) proteins of WM164 and HT144 cells in a drug-tolerant state (DTP; 28 days with 100 nM dabrafenib) or a permanent drug-resistant state (PDR; ≥ 105 days with 100 nM dabrafenib) compared with untreated cells. P-value ≤ 0.05; log2 fold change ± 1; (B) Diagrams of WM164 and HT144 DTP with the number (end of each bar) of upregulated (red) and downregulated (blue) proteins involved in identified KEGG pathways (https://www.genome.jp/kegg/pathway.html) with P-value ≤ 0.05; log2 fold change ± 1 (fold enrichment: enrichment factor calculated as a quotient of number of found proteins and number of expected proteins). See also Supplementary Figure 5; (C) GO functional analysis of differentially expressed proteins in WM164 and HT144 DTPs. Proteins of DTPs were compared to proteins from drug-naïve cells. Histograms represent fold enrichment of the top 5 differentially expressed proteins (P-value ≤ 0.05; log2 fold change ± 1) involved in molecular function (blue), biological process (yellow) and cellular component (purple) categories. See also Supplementary Figure 6; (D) Heat map showing downregulated (blue) and upregulated (red) proteins in key lipid synthesis and metabolic pathways. Colours indicate log2 fold change of expressed proteins in WM164 and HT144 cells in the DTP or PDR states relative to drug-naïve cells. See also Supplementary File 3. DTP: Drug-tolerant persister; PDR: permanent drug-resistant; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: gene ontology; FA: fatty acid; PI: phosphatidylinositol.