Extended Data Fig. 9: PRRX1 is a master regulator of the mesenchymal-like transcriptional program.
a, Violin plots depict conserved Prrx1 regulon activity scores (AUCell) across mouse Seurat clusters. b, Violin plots depict conserved PRRX1 regulon activity scores (AUCell) across human Seurat clusters. c, PRRX1 expression in n=375 TCGA_SKCM patients stratified as invasive (n=123), immune-related (n=116) and proliferative (n=136) phenotypes based on their gene expression profile described previously35. Box plots summarize the values per phenotypic group and show the median. Boxes extend from the 25th to 75th percentiles, whiskers and outliers were plotted according to the Tukey method. Significance was assessed by an unpaired nonparametric, two-tailed Mann-Whitney Test (approximate p value, p<0.0001). d, Heatmap generated using the TCGA database illustrating the gene expression profile of patients with PRRX1 high and low expression (20th percentile cut-off). Genes from the conserved PRRX1 regulon are co-expressed together with PRRX1. e, Left panel, PRRX1 expression (226695_at) in invasive (n=71) and proliferative (n=81) melanoma cell lines as previously described36. Error bars represent ±SEM. Significance was assessed by an unpaired nonparametric, two-tailed Mann-Whitney Test (approximate P value, p<0.0001). Right panel, qPCR analysis for PRRX1 in short term melanoma cells lines categorized as proliferative (n=11) and invasive (n=7) based on their gene expression profile). Error bars represent ±SEM. Significance was assessed by unpaired nonparametric two-tailed Student’s t-test. (p = 0.1509). f, PRRX1 expression (upper panel) and signature activity (lower panel) in short term proliferative/melanocytic melanoma cell lines (MM057, MM074 and MM087) transfected with SOX10 siRNA or non-targeting control. Baseline refers to the non-transfected melanoma cell lines. g, Left panel, matrigel-invasion assay upon silencing of PRRX1 in MM099 cells. Right panel, quantification (n=3; p=0.0011). h, Relative mRNA expression of PRRX1 upon siPRRX1 (n=3; p=0.0003). In g and h significance was assessed by unpaired two-tailed Student’s t-test.