MITF Reprograms the Extracellular Matrix and Focal Adhesion in Melanoma

Overview

Journal Elife

Specialty Biology

Date 2021 Jan 13

PMID 33438577

Citations 44

Authors

Ramile Dilshat

Valerie Fock

Colin Kenny

Ilse Gerritsen

Romain Maurice Jacques Lasseur

Jana Travnickova

Ossia M Eichhoff

Philipp Cerny

Katrin Moller

Sara Sigurbjornsdottir

Kritika Kirty

Berglind Osk Einarsdottir

Phil F Cheng

Mitchell Levesque

Robert A Cornell

E Elizabeth Patton

Lionel Larue

Marie de Tayrac

Erna Magnusdottir

Margret Helga Ogmundsdottir

Eirikur Steingrimsson

Affiliations

Soon will be listed here.

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.

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