NDLI: MITF reprograms the extracellular matrix and focal adhesion in melanoma

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Ramile Dilshat Valerie Fock Colin Kenny Ilse Gerritsen Romain Maurice Jacques Lasseur Jana Travnickova Ossia M. Eichhoff Philipp Cerny Katrin Möller Sara Sigurbjörnsdóttir Kritika Kirty Berglind Ósk Einarsdottir Phil F. Cheng Mitchell Levesque Robert A. Cornell E. Elizabeth Patton Lionel Larue Marie de Tayrac Erna Magnúsdóttir Margrét Helga Ögmundsdóttir Eirikur Steingrimsson
Abstract	The microphthalmia-associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here, we show that MITF directly represses the expression of genes associated with the extracellular matrix (ECM) and focal adhesion pathways in human melanoma cells as well as of regulators of epithelial-to-mesenchymal transition (EMT) such as CDH2, thus affecting cell morphology and cell-matrix interactions. Importantly, we show that these effects of MITF are reversible, as expected from the rheostat model. The number of focal adhesion points increased upon MITF knockdown, a feature observed in drug-resistant melanomas. Cells lacking MITF are similar to the cells of minimal residual disease observed in both human and zebrafish melanomas. Our results suggest that MITF plays a critical role as a repressor of gene expression and is actively involved in shaping the microenvironment of melanoma cells in a cell-autonomous manner.
e-ISSN	2050084X
DOI	10.7554/eLife.63093
Journal	eLife
Volume Number	10
Language	English
Publisher	eLife Sciences Publications Ltd
Publisher Date	2021-01-01
Publisher Place	United Kingdom
Access Restriction	Open
Subject Keyword	Medicine Science Biology (general) Melanoma Extracellular Matrix Mitf Focal Adhesion Repression
Content Type	Text
Resource Type	Article

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