biostudies-literatureUnknown35(5)Chauhan JSFonds de Recherche du Québec-SantéCancer Research Society and Genome QuebecCancer Research UKDeutsche KrebshilfeLudwig Institute for Cancer ResearchBidirectional interactions between plastic tumor cells and the microenvironment critically impact tumor evolution and metastatic dissemination by enabling cancer cells to adapt to microenvironmental stresses by switching phenotype. In melanoma, a key determinant of phenotypic identity is the microphthalmia-associated transcription factor MITF that promotes proliferation, suppresses senescence, and anticorrelates with immune infiltration and therapy resistance. What determines whether MITF can activate or repress genes associated with specific phenotypes, or how signaling regulating MITF might impact immune infiltration is poorly understood. Here, we find that MITF binding to genes associated with high MITF is via classical E/M-box motifs, but genes downregulated when MITF is high contain FPigment cell & melanoma research517-533https://www.ebi.ac.uk/biostudies/studies/S-EPMC9545041biostudies-literatureThe MITF regulatory network in melanoma.PMC9545041Holzel MBuffa FMLambert JPChauhan JSGoding CRfalseThe MITF regulatory network in melanoma.Bidirectional interactions between plastic tumor cells and the microenvironment critically impact tumor evolution and metastatic dissemination by enabling cancer cells to adapt to microenvironmental stresses by switching phenotype. In melanoma, a key determinant of phenotypic identity is the microphthalmia-associated transcription factor MITF that promotes proliferation, suppresses senescence, and anticorrelates with immune infiltration and therapy resistance. What determines whether MITF can activate or repress genes associated with specific phenotypes, or how signaling regulating MITF might impact immune infiltration is poorly understood. Here, we find that MITF binding to genes associated with high MITF is via classical E/M-box motifs, but genes downregulated when MITF is high contain F2022-01-01T00:00:00Z2022 Sep2025-04-22T01:56:37.531Z2025-04-05T20:12:34.449ZS-EPMC95450413577117910.1111/pcmr.13053