Fig. 6: YAP activation promotes melanomagenesis.

a GSEA performed on GSE61750 comparing enrichment of YAP/TAZ signatures in melanoma to arrested melanocytes in indicated genotype (see Supplementary Fig. S7A, S7D). b Left, representative IB of Mel-ST parental cell line treated with control siRNA (siC) or LATS1 and LATS2 siRNAs (siLATS); right, quantification of PTEN and p-S6 proteins compared to loading control or total protein (n = 3 independent experiments, graphs show mean ± SEM, two-tailed unpaired t test). c Top, representative IB of Mel-ST parental cell line expressing indicated plasmids, EV: empty vector; bottom, quantification of PTEN compared to loading control (n = 2 independent experiments, graph shows mean). d IB comparing D4M.3 A cells and Lats1/2^−/− tumor lysates where numbers represent replicates or different tumors, respectively (n = 3 independent experiments or mice). e Left, survival curve of zebrafish with indicated genotypes; right, representative images of zebrafish with indicated genotype (n = 14 independent EGFP fish, n = 10 independent YAP-5SA fish, log-rank test). f Graph shows relative viability decrease (%) in indicated cell lines treated with 10 µM MGH-CP1 for 4 days (n = 3 independent experiments in ≥technical quintuplicate, graph shows mean ± SEM, one-way ANOVA with Dunnett’s multiple comparisons test). g Schematic model in which we propose overproliferation of melanocytes following acquisition of oncogenic BRAF^V600E leads to increases in local melanocyte density, which subsequently promotes Hippo pathway activation and contributes to growth arrest and nevus formation. Functional impairment of the Hippo pathway, leading to YAP/TAZ activation, enables melanocytes expressing BRAF^V600E to evade stable growth arrest and promote the development of melanoma. Source Data are provided as a Source Data file.