MAFG: A key regulator in melanoma progression and a potential therapeutic target

The MAF bZIP Transcription Factor G (MAFG) is a member of the small MAF family of proteins. Previously, we have shown that miRNA-29 suppresses melanoma development, at least in part, by repressing MAFG expression. In addition, analysis of the TCGA revealed frequent amplification and/or overexpression of MAFG in melanoma. However, despite the known roles of MAFG in regulating antioxidant responses, its cell-intrinsic and -extrinsic effects in melanoma are unknown. Here, we investigated the role of MAFG in melanomagenesis. MAFG expression increases with human melanoma stages, and ectopic MAFG expression enhances the malignant behavior of human melanoma cells in vitro, in xenograft models, and in genetic mouse models of spontaneous melanoma. Moreover, MAFG induces a melanoma phenotype switch from a melanocytic state to a more dedifferentiated state. Mechanistically, MAFG interacts with the lineage transcription factor MITF, which is required for the cell-intrinsic pro-tumorigenic effects of MAFG. Furthermore, we discovered that MAFG regulates transcriptional programs associated with the remodel of the extracellular matrix (ECM). Collectively, our study demonstrates that MAFG plays a pivotal role in melanomagenesis, and future studies will address if MAFG can be used as a therapeutic target.

 

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