PUBLICATION
Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells
- Authors
- Franzetti, G.A., Laud-Duval, K., van der Ent, W., Brisac, A., Irondelle, M., Aubert, S., Dirksen, U., Bouvier, C., de Pinieux, G., Snaar-Jagalska, E., Chavrier, P., Delattre, O.
- ID
- ZDB-PUB-170916-12
- Date
- 2017
- Source
- Oncogene 36: 3505-3514 (Journal)
- Registered Authors
- Snaar-Jagalska, Ewa B., van der Ent, Wietske
- Keywords
- none
- MeSH Terms
-
- Animals
- Calmodulin-Binding Proteins/biosynthesis*
- Calmodulin-Binding Proteins/genetics
- Cell Line, Tumor
- Cell Movement*
- Cell Proliferation*
- Gene Expression Regulation, Neoplastic*
- Mice
- Mice, SCID
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Oncogene Proteins, Fusion/biosynthesis*
- Oncogene Proteins, Fusion/genetics
- Proto-Oncogene Protein c-fli-1/biosynthesis*
- Proto-Oncogene Protein c-fli-1/genetics
- RNA-Binding Proteins/biosynthesis*
- RNA-Binding Proteins/genetics
- Sarcoma, Ewing/genetics
- Sarcoma, Ewing/metabolism*
- Sarcoma, Ewing/pathology
- Zebrafish
- PubMed
- 28135250 Full text @ Oncogene
Citation
Franzetti, G.A., Laud-Duval, K., van der Ent, W., Brisac, A., Irondelle, M., Aubert, S., Dirksen, U., Bouvier, C., de Pinieux, G., Snaar-Jagalska, E., Chavrier, P., Delattre, O. (2017) Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells. Oncogene. 36:3505-3514.
Abstract
Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix adhesion. These changes are associated with a dramatic increase of in vivo cell migration and invasion potential. Importantly, EWSR1-FLI1 expression, evaluated by single-cell RT-ddPCR/immunofluorescence analyses, and activity, assessed by expression of EWSR1-FLI1 downstream targets, are heterogeneous in cell lines and in tumours and can fluctuate along time in a fully reversible process between EWSR1-FLI1high states, characterized by highly active cell proliferation, and EWSR1-FLI1low states where cells have a strong propensity to migrate, invade and metastasize. This new model of phenotypic plasticity proposes that the dynamic fluctuation of the expression level of a dominant oncogene is an intrinsic characteristic of its oncogenic potential.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping