Year: 2026
Type: article
Abstract: Phenotype switching, a key driver of melanoma progression and therapy resistance, is governed by the lineage transcription factor MITF. Here, we identify the small MAF family transcription factor MAFG as a critical regulator of MITF activity and melanoma cell state plasticity. MAFG expression is frequently elevated in melanoma and correlates with poor patient survival. Mechanistically, MAFG binds MITF and redirects its genomic occupancy, thereby modulating transcriptional programs governed by MITF. Genetic perturbation studies in vitro and in vivo show that MAFG promotes a dedifferentiated cell state and accelerates melanoma progression through its direct interaction with MITF. Moreover, MAFG is required for melanoma cell proliferation and for the transition from nevi to melanoma in genetic mouse models. Together, these findings demonstrate that the MAFG~MITF complex orchestrates phenotype switching and tumor progression, uncovering an unrecognized mechanism of MITF regulation in melanoma.
Source: Nature Communications
Authors: Olga Vera, Michael Martinez, Zulaida Soto-Vargas, Kaizhen Wang, Xiaonan Xu, Nicol Mecozzi, Harini Murikipudi, Sara Ruiz-Buceta, Manon Chadourne, Benjamin Posorske, Ariana Angarita, Ilah Bok, Juan D. Ulloa Arrieta, Qian Liu, Yumi Kim, Jane L. Messina, Kenneth Y. Tsai, Michael B. Major, Eric K. Lau, Xiaoqing Yu, Inmaculada Ibanez de Caceres, Florian A. Karreth
Institutions: Hospital Universitario La Paz, Moffitt Cancer Center, Hospital La Paz Institute for Health Research, University of South Florida, Inserm, Centre Méditerranéen de Médecine Moléculaire, A.T. Still University, Washington University in St. Louis, Oregon Health & Science University, OHSU Knight Cancer Institute
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G2931208492, Caracterización de epi-marcadores de la rigidez del estroma tumoral en vesículas extracelulares en cáncer de pulmón no microcítico, G5556285564, G5721667682, G5938941316, G6217714277, Exploring miR-29 in melanoma progression and prevention, Estudio de la Plasticidad Tumoral Epigenética a través de la carcinogénesis y progresión del CPNM en biopsia líquida. SETuP., G8352736059, G9000252334, G9000332026, Molecular Oncology Training Grant, Moffitt Cancer Center Support Grant, Drugging NRF2 to improve radiation therapy in head and neck squamous cell carcinoma
OpenAlex ID: W7162015463
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