Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma

Given the heterogeneous expression of SOX10 in naive melanoma, we sought to characterize SOX10 deficient population. To this end, we generated SOX10 CRISPR/Cas9 knockouts using two different single guide RNA (sgRNA, #2 and #4) in the MeWo (wild-type for BRAF and NRAS) metastatic cell line. Using this approach, we identified multiple clones with loss of SOX10 expression. RNA-seq was performed to characterize the SOX10-regulated transcriptome. We used GSEA analysis to evaluate significant pathway changes in SOX10 knockout cells when compared to parental cells. We observed an enrichment in pathways associated with the tumor microenvironment (epithelial-mesenchymal transition; TGF beta signaling; extracellular structure organization; apical junction; hypoxia; angiogenesis), alterations in metabolic pathways (increase in the glycolysis pathway), a reduction in MYC and E2F targets and upregulation in p53 pathway and TNFA signaling via NFkB in the SOX10 knockout cells compared to parental cells.