Figure 5 from p300 KAT Regulates SOX10 Stability and Function in Human Melanoma

A-485 potently inhibits proliferation of SOX10⁺ melanoma cell lines. A, A panel of melanoma cell lines were treated with A-485 (in a range of doses) for 6 days, and their relative proliferation vs. control was assessed (left). The results for 5 µmol/L A-485 vs. control are shown (right). B, Cells that did not respond to A-485 within 6 days were pretreated with 5 µmol/L A-485 for 9 days and reseeded for a 3-day proliferation assay, and their relative proliferation vs. control was assessed (total 12 days of drug treatment). C, WM983B-R and SK-Mel-28-R BRAFi-resistant cells have low expression of SOX10 in comparison with parental cells. D, The proliferation effects of short-term (6-day) or long-term (12-day) A-485 treatment of WM983B-R and SK-Mel-28-R cells were assessed. E, 451Lu-R cells maintain SOX10 expression vs. BRAFi-sensitive parental cells (left). 451Lu-S and 451Lu-R were treated with A-485 (in a range of doses) for 6 days, and their relative proliferation vs. control was assessed (right). F, A375-R cells maintain SOX10 expression vs. BRAFi-sensitive parental cells (left). A375-S and A375-R cells were treated with A-485 (in a range of doses) for 6 days, and their relative proliferation vs. control was assessed (middle). A375-S and A375-R cells were pretreated 5 µmol/L A-485 for 9 days and reseeded for a 3-day proliferation assay, and their relative proliferation vs. control was assessed (right). G, EP300 dependency scores are plotted for melanoma cell lines with low SOX10 [<4 log₂(TPM + 1)] vs. high SOX10 [>4 log₂(TPM + 1)] expression in the CDM 22Q2 public + score, Chronos dataset. *, P < 0.05; **, P < 0.005; ***, P < 0.0005.