Figure 6. Inhibition of the CoREST complex in BRAFi-R melanoma cells promotes transcriptional changes associated with the phenotype switch and increased expression of DUSP family MAPK inhibitors.

(A) Heatmap of differential expression patterns of proliferative versus invasive gene signatures and transcriptional regulators associated with distinct melanoma phenotypes²² (indicated by a red asterisk) in 451Lu-R and 1205Lu-R melanoma cells treated with 2.5 μM corin or DMSO for 24 hours. (B) Comparison of the corin-associated intermediate phenotype gene expression signature in 451Lu-R and 1205Lu-R melanoma cells treated with 2.5 μM corin or DMSO for 24 hours and the published intermediate phenotype defined by Wouters et al. (26). (C) Volcano plots of differentially expressed genes (DEGs) (log₂ FC >1, Padj < 0.01) in 451Lu-R (left) and 1205Lu-R (right) melanoma cells following 24 hours of treatment with 2.5 μM corin plus 5 μM PLX4032 versus 5 μM PLX4032 alone with highlighted changes in DUSP1, DUSP5, MITF, and AXL expression. (D) Heatmap of DUSP1/-4/-5/-6 expression in corin-treated BRAFi-S melanoma cells relative to DMSO treatment (2.5 μM, 24 hours). (E) Top known transcription factor–binding motifs enriched in corin-upregulated genes in 451Lu-R (left) and 1205Lu-R (right) melanoma cells.