PUBLICATION
MITF reprograms the extracellular matrix and focal adhesion in melanoma
- Authors
- Dilshat, R., Fock, V., Kenny, C., Gerritsen, I., Lasseur, R.M.J., Travnickova, J., Eichhoff, O.M., Cerny, P., Möller, K., Sigurbjörnsdóttir, S., Kirty, K., Einarsdottir, B.Ó., Cheng, P.F., Levesque, M., Cornell, R.A., Patton, E.E., Larue, L., de Tayrac, M., Magnúsdóttir, E., Helga Ögmundsdóttir, M., Steingrimsson, E.
- ID
- ZDB-PUB-210114-15
- Date
- 2021
- Source
- eLIFE 10: (Journal)
- Registered Authors
- Cornell, Robert, Kenny, Colin, Möller, Katrin, Patton, E. Elizabeth, Sigurbjörnsdóttir, Sara
- Keywords
- cancer biology, genetics, genomics, human
- MeSH Terms
-
- Cell Line, Tumor
- Epithelial-Mesenchymal Transition*
- Extracellular Matrix/metabolism*
- Focal Adhesions/metabolism*
- Humans
- Melanoma/metabolism
- Microphthalmia-Associated Transcription Factor/genetics*
- Microphthalmia-Associated Transcription Factor/metabolism
- PubMed
- 33438577 Full text @ Elife
Citation
Dilshat, R., Fock, V., Kenny, C., Gerritsen, I., Lasseur, R.M.J., Travnickova, J., Eichhoff, O.M., Cerny, P., Möller, K., Sigurbjörnsdóttir, S., Kirty, K., Einarsdottir, B.Ó., Cheng, P.F., Levesque, M., Cornell, R.A., Patton, E.E., Larue, L., de Tayrac, M., Magnúsdóttir, E., Helga Ögmundsdóttir, M., Steingrimsson, E. (2021) MITF reprograms the extracellular matrix and focal adhesion in melanoma. eLIFE. 10:.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping