Fig. 8: YAP1/TAZ-TEAD signaling up-regulation is TAZ-dependent in acquired resistant melanoma cell lines.
A Enrichment plots of mesenchymal signature38 for CRT34 and CRT35, and PBRT15 and PBRT16, cells compared vs parental cells.  ***p < 0.001 two-tailed BHFDR. B Heatmap showing GSEA of YAP1/TAZ gene signatures comparing parental A375 and 1205Lu cell lines to drug-tolerant cell lines. *p < 0.05, **p < 0.01, ***p < 0.001 two-tailed BHFDR. C A375 parental, CRT34, CRT35, A375 2.18 SOX10 KO, and A375 4.21 SOX10 KO cells were plated and left untreated. Cell lysates were analyzed by Western blotting with the antibodies indicated. The experiment was repeated independently three times with similar results. D CRT34 or CRT35 cells were treated with reagent alone, non-targeting control siRNA, siYAP1, or siTAZ for 72 hrs. Lysates were analyzed by Western blotting with the antibodies indicated. The experiment was repeated independently three times with similar results. E A375 parental, CRT34, and CRT35 cells were treated with 2 µM of either OPN-9652 or OPN-9643 for 48 hrs. Cells were lysed, and lysates were analyzed by Western blotting with the antibodies indicated. The experiment was repeated independently three times with similar results. F 4.21 SOX10 KO cells were injected into NSG mice. Once tumors reached 100 mm3, mice received either OPN-9652 (50 mg/kg) for 3 days or vehicle. Tumors were harvested and analyzed by Western blotting with the antibodies indicated. G Quantification of CYR61 expression performed in ImageLab using volume tools to calculate CYR61 compared to HSP90 loading control. Data are expressed as mean ± SD Vehicle n = 4, OPN-6952 n = 5. *p < 0.05, Welch’s two-tailed unpaired t-test. H Mean tumor growth graph comparing treatment arms of A375 xenograft treated with PLX4720 (200 PPM),  PD0325901 (7 PPM) alone (6 mice) or in combination with OPN-9652 (50 mg/kg) (7 mice). Data are expressed as mean ± SEM. Welch’s two-tailed t-test. Source Data are available. I Mouse survival curves from experiment in Fig. 8H, indicating time for tumor to reach 1000 mm3. Censored mice were due to unexplained deaths. P value was calculated using Logrank (Mantel-Cox) test. Source Data are available.
