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MITF has a central role in regulating starvation-induced autophagy in melanoma

MITF has a central role in regulating starvation-induced autophagy in melanoma

Title: MITF has a central role in regulating starvation-induced autophagy in melanoma
Author: Möller, Katrin   orcid.org/0000-0002-4720-8568
Sigurbjornsdottir, Sara   orcid.org/0000-0002-3030-8888
Arnþórsson, Ásgeir O.
Pogenberg, Vivian
Dilshat, Ramile   orcid.org/0000-0002-2126-2902
Fock, Valerie   orcid.org/0000-0002-7812-4340
Brynjólfsdóttir, Sólveig Hlín   orcid.org/0000-0003-0554-3613
Bindesboll, Christian
Bessadóttir, Margrét   orcid.org/0000-0002-9750-8892
Ögmundsdóttir, Helga M.
... 6 more authors Show all authors
Date: 2019-01-31
Language: English
Scope: 1055
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Lífvísindasetur (HÍ)
Biomedical Center (UI)
Series: Scientific Reports;9(1)
ISSN: 2045-2322
DOI: 10.1038/s41598-018-37522-6
Subject: Macroautophagy; Melanoma; Genarannsóknir; Húðkrabbamein
URI: https://hdl.handle.net/20.500.11815/1577

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Möller, K., Sigurbjornsdottir, S., Arnthorsson, A.O. et al. MITF has a central role in regulating starvation-induced autophagy in melanoma. Sci Rep 9, 1055 (2019). https://doi.org/10.1038/s41598-018-37522-6


The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEARbox element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells. The crystal structure of MITF bound to the CLEAR-box reveals how the palindromic nature of this motif induces symmetric MITF homodimer binding. In metastatic melanoma tumors and cell lines, MITF positively correlates with the expression of lysosomal and autophagosomal genes, which, interestingly, are diferent from the lysosomal and autophagosomal genes correlated with TFEB and TFE3. Depletion of MITF in melanoma cells and melanocytes attenuates the response to starvation-induced autophagy, whereas the overexpression of MITF in melanoma cells increases the number of autophagosomes but is not sufcient to induce autophagic fux. Our results suggest that MITF and the related factors TFEB and TFE3 have separate roles in regulating a starvation-induced autophagy response in melanoma. Understanding the normal and pathophysiological roles of MITF and related transcription factors may provide important clinical insights into melanoma therapy.


Publisher's version (útgefin grein). Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-37522-6.


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