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In addition, the AP-1 family member c-Jun is highly active in melanoma cells, and its expression is negatively regulated by MITF, which binds to the JUN promoter and blocks its transcription ( V600E -mutant melanoma cells leads to increased c-Jun expression, resulting in mesenchymal-like phenotype and resistance to BRAF/MEK inhibitors (MAPKi) ( SPROUTY4 downregulation, which leads to increased abundance of c-Jun and a subsequent switch to the mesenchymal-like and drug-resistant state ( FOSL1 ), downregulates MITF through its transcriptional target, the chromatin modifier HMGA1, and induces the expression of AXL, driving melanoma cells to the MITF low /AXL high state (53)