MITF regulates IDH1, NNT, and a transcriptional program protecting melanoma from reactive oxygen species.

Autor: Roider E; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA. Elisabeth.Roider@usb.ch.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA. Elisabeth.Roider@usb.ch.; Department of Dermatology, University Hospital of Basel, Basel, Switzerland. Elisabeth.Roider@usb.ch., Lakatos AIT; HCEMM-SU Translational Dermatology Research Group, Semmelweis University, Budapest, Hungary.; Department of Physiology, Semmelweis University, Budapest, Hungary.; Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, Hungary., McConnell AM; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Massachusetts and the Howard Hughes Medical Institute, Boston, USA., Wang P; Department of Pharmaceutical Sciences, Department of Chemistry and Chemical Biology, and Barnett Institute, Bouve College, Northeastern University, Boston, MA, 02115, USA., Mueller A; Department of Dermatology, University Hospital of Basel, Basel, Switzerland., Kawakami A; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA., Tsoi J; Department of Molecular and Medical Pharmacology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.; UCLA Metabolomics Center, University of California, Los Angeles (UCLA), Los Angeles, CA, USA., Szabolcs BL; HCEMM-SU Translational Dermatology Research Group, Semmelweis University, Budapest, Hungary.; Department of Physiology, Semmelweis University, Budapest, Hungary.; Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, Hungary., Ascsillán AA; HCEMM-SU Translational Dermatology Research Group, Semmelweis University, Budapest, Hungary.; Department of Physiology, Semmelweis University, Budapest, Hungary.; Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, Hungary., Suita Y; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA., Igras V; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA., Lo JA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA., Hsiao JJ; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA., Lapides R; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.; Robert Larner, College of Medicine at the University of Vermont, Burlington, USA., Pál DMP; HCEMM-SU Translational Dermatology Research Group, Semmelweis University, Budapest, Hungary.; Department of Physiology, Semmelweis University, Budapest, Hungary.; Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, Hungary., Lengyel AS; HCEMM-SU Translational Dermatology Research Group, Semmelweis University, Budapest, Hungary.; Department of Physiology, Semmelweis University, Budapest, Hungary.; Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, Hungary., Navarini A; Department of Dermatology, University Hospital of Basel, Basel, Switzerland., Okazaki A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA., Iliopoulos O; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA., Németh I; Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary., Graeber TG; Department of Molecular and Medical Pharmacology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.; UCLA Metabolomics Center, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.; Crump Institute for Molecular Imaging, UCLA, Los Angeles, CA, USA., Zon L; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Massachusetts and the Howard Hughes Medical Institute, Boston, USA., Giese RW; Department of Pharmaceutical Sciences, Department of Chemistry and Chemical Biology, and Barnett Institute, Bouve College, Northeastern University, Boston, MA, 02115, USA., Kemeny LV; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA. Kemeny.lajos@semmelweis.hu.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA. Kemeny.lajos@semmelweis.hu.; HCEMM-SU Translational Dermatology Research Group, Semmelweis University, Budapest, Hungary. Kemeny.lajos@semmelweis.hu.; Department of Physiology, Semmelweis University, Budapest, Hungary. Kemeny.lajos@semmelweis.hu.; Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, Hungary. Kemeny.lajos@semmelweis.hu., Fisher DE; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA. dfisher3@mgh.harvard.edu.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA. dfisher3@mgh.harvard.edu.; Lancer Professorship of Dermatology, Harvard Medical School, Boston, USA. dfisher3@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Sep 14; Vol. 14 (1), pp. 21527. Date of Electronic Publication: 2024 Sep 14.
DOI: 10.1038/s41598-024-72031-9
Abstrakt: Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte function, development and plays a significant role in melanoma pathogenesis. MITF genomic amplification promotes melanoma development, and it can facilitate resistance to multiple therapies. Here, we show that MITF regulates a global antioxidant program that increases survival of melanoma cell lines by protecting the cells from reactive oxygen species (ROS)-induced damage. In addition, this redox program is correlated with MITF expression in human melanoma cell lines and patient-derived melanoma samples. Using a zebrafish melanoma model, we show that MITF decreases ROS-mediated DNA damage in vivo. Some of the MITF target genes involved, such as IDH1 and NNT, are regulated through direct MITF binding to canonical enhancer box (E-BOX) sequences proximal to their promoters. Utilizing functional experiments, we demonstrate the role of MITF and its target genes in reducing cytosolic and mitochondrial ROS. Collectively, our data identify MITF as a significant driver of the cellular antioxidant state.
(© 2024. The Author(s).)
Databáze: MEDLINE
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