{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dias D"],"funding":["China Scholarship Council","Fundación Séneca","Ludwig Institute for Cancer Research Ltd","Melanoma Research Alliance","NCI NIH HHS","Community of Madrid","España Ministerio de Ciencia Innovación y Universidades","National Institutes of Health","State Agency of Research","Caixabank SA","State of Sao Paulo Research Foundation","American Cancer Society Inc"],"pagination":["116499"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12828906"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(12)"],"pubmed_abstract":["Cells can contain multiple related transcription factors targeting the same sequences, leading to potential regulatory cooperativity, redundancy, competition, or temporally regulated factor exchange. Yet, the differential biological functions of co-targeting transcription factors are poorly understood. In melanoma, three highly related transcription factors are co-expressed: the mammalian target of rapamycin complex 1 (mTORC1)-regulated TFEB and TFE3 (both key effectors of a wide range of metabolic and microenvironmental cues assumed to perform similar functions) and the microphthalmia-associated transcription factor (MITF), which controls melanoma phenotypic identity. Here, we reveal the functional specialization of MITF, TFE3, and TFEB and their impact on melanoma progression. Notably, although all bind the same sequences, each regulates different and frequently opposing gene expression programs to coordinate differentiation, metabolism, and protein synthesis and qualitatively and quantitatively impacts tumor immune infiltration. The results uncover a hierarchical cascade whereby microenvironmental stresses, including glucose limitation, lead MITF, TFEB, and TFE3 to drive distinct biologically important transcription programs that underpin phenotypic transitions in cancer."],"journal":["Cell reports"],"pubmed_title":["MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma."],"pmcid":["PMC12828906"],"funding_grant_id":["R01 CA268597","P01 CA128814"],"pubmed_authors":["Bellini A","Mosteo L","Dias D","Sanchez-Del-Campo L","Chauhan J","Rodriguez-Lopez JN","Marti-Diaz R","Garcia-Martinez JM","Kenny C","Garcia YV","Li L","Chocarro-Calvo A","Garcia-Jimenez C","Andrews S","Louphrasitthiphol P","Oliveira E","Maria-Engler SS","Martinez-Useros J","Goding CR"],"additional_accession":[]},"is_claimable":false,"name":"MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma.","description":"Cells can contain multiple related transcription factors targeting the same sequences, leading to potential regulatory cooperativity, redundancy, competition, or temporally regulated factor exchange. Yet, the differential biological functions of co-targeting transcription factors are poorly understood. In melanoma, three highly related transcription factors are co-expressed: the mammalian target of rapamycin complex 1 (mTORC1)-regulated TFEB and TFE3 (both key effectors of a wide range of metabolic and microenvironmental cues assumed to perform similar functions) and the microphthalmia-associated transcription factor (MITF), which controls melanoma phenotypic identity. Here, we reveal the functional specialization of MITF, TFE3, and TFEB and their impact on melanoma progression. Notably, although all bind the same sequences, each regulates different and frequently opposing gene expression programs to coordinate differentiation, metabolism, and protein synthesis and qualitatively and quantitatively impacts tumor immune infiltration. The results uncover a hierarchical cascade whereby microenvironmental stresses, including glucose limitation, lead MITF, TFEB, and TFE3 to drive distinct biologically important transcription programs that underpin phenotypic transitions in cancer.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-06T22:07:06.479Z","creation":"2026-06-05T03:12:10.886Z"},"accession":"S-EPMC12828906","cross_references":{"pubmed":["41275493"],"doi":["10.1016/j.celrep.2025.116499"]}}