Journal article
MITF reprograms the extracellular matrix and focal adhesion in melanoma
eLife, Vol.10, pp.1-59
01/13/2021
DOI: 10.7554/eLife.63093
PMCID: PMC7857731
PMID: 33438577
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.
Details
- Title: Subtitle
- MITF reprograms the extracellular matrix and focal adhesion in melanoma
- Creators
- Ramile Dilshat - University of IcelandValerie Fock - University of IcelandColin Kenny - Roy J. and Lucille A. Carver College of MedicineIlse Gerritsen - University of IcelandRomain Maurice Jacques Lasseur - University of IcelandJana Travnickova - Institute of Genetics and CancerOssia M. Eichhoff - University Hospital of ZurichPhilipp Cerny - University of IcelandKatrin Moller - University of IcelandSara Sigurbjornsdottir - University of IcelandKritika Kirty - University of IcelandBerglind Osk Einarsdottir - University of IcelandPhil F. Cheng - University Hospital of ZurichMitchell Levesque - University Hospital of ZurichRobert A. Cornell - Roy J. and Lucille A. Carver College of MedicineE. Elizabeth Patton - Institute of Genetics and CancerLionel Larue - Institut CurieMarie de Tayrac - Institut de génétique et de développement de RennesErna Magnusdottir - University of IcelandMargret Helga Ogmundsdottir - University of IcelandEirikur Steingrimsson - University of Iceland
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.10, pp.1-59
- DOI
- 10.7554/eLife.63093
- PMID
- 33438577
- PMCID
- PMC7857731
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Publisher
- Elife Sciences Publications Ltd
- Number of pages
- 30
- Grant note
- A2062457 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA MC_UU_00007/9 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 184861 / Icelandic Centre for Research 401181 / L'Oreal Melanoma Research Alliance ZF-MEL-CHEMBIO-648489 / European Research Council; European Research Council (ERC); European Commission MC_UU_00007/9 E; HI16120042 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 687306 / Anna-Maria and Stephen Kellen Foundation-Melanoma Research Alliance Team Science Award
- Language
- English
- Date published
- 01/13/2021
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9984322827102771
Metrics
28 Record Views