1279 MITF-regulates cellular ROS levels in cutaneous melanoma

Microphthalmia-associated transcription factor (MITF) plays a pivotal role in melanocyte development and function as well melanoma pathogenesis. MITF amplification is common has been associated with resistance to targeted therapies. Melanin, whose synthesis largely regulated by MITF, powerful anti-oxidant activity. Here we show that additionally regulates transcriptional antioxidant program increases survival of cell lines protecting the cells from reactive oxygen species (ROS)-induced damage. In addition, this redox correlates expression human patient-derived samples. A zebrafish model verified decreases ROS-mediated DNA damage vivo. Some target genes, such IDH1 NNT, are through direct binding canonical E-BOX sequences proximal their promoters. its genes reduce cytosolic mitochondrial ROS cells. Collectively, these data suggest major driver cellular state may offer potential novel therapeutic approaches melanoma.