ArticleDisease models & mechanisms2012
A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.
Article in Disease models & mechanisms, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
- Modeling of Capicua Family Fusion Oncoprotein-Driven Cancers Reveals Gene-Specific Functionality.Molecular cancer research : MCR · 2026Article
- Tissue-Specific Expression of the EWSR1::FLI1 Fusion Protein IdentifiesInternational journal of molecular sciences · 2026Article
- Beyond the mouse: 3R-guided alternative animal models transforming cancer research.Molecular cancer · 2026Review
- Genome-wide association study meta-analysis identifies susceptibility loci informing Ewing sarcoma etiology and potential mechanisms of risk.medRxiv : the preprint server for health sciences · 2026Article
- Choosing the right animal model for sarcoma research.Cellular and molecular life sciences : CMLS · 2026Review
- YAP1 is a key regulator of EWS::FLI1-dependent malignant transformation upon IGF-1-mediated reprogramming of bone mesenchymal stem cells.Cell reports · 2025Article
- Small Fish, Big Answers: Zebrafish and the Molecular Drivers of Metastasis.International journal of molecular sciences · 2025Review
- Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research.Biomedicines · 2024Review
- Functional Genomics of Novel Rhabdomyosarcoma Fusion-Oncogenes Using Zebrafish.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Preclinical models for the study of pediatric solid tumors: focus on bone sarcomas.Frontiers in oncology · 2024Review
- Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.The Science of the total environment · 2023Review
- Modeling Ewing Sarcoma Lung Metastasis.Current protocols · 2023Article
- Human EWS-FLI protein recapitulates in Drosophila the neomorphic functions that induce Ewing sarcoma tumorigenesis.PNAS nexus · 2022Article
- Inhibitor of DNA binding 2 (ID2) regulates the expression of developmental genes and tumorigenesis in ewing sarcoma.Oncogene · 2022Article
- Dysregulated heparan sulfate proteoglycan metabolism promotes Ewing sarcoma tumor growth.eLife · 2022Article
- Ewing Sarcoma-Diagnosis, Treatment, Clinical Challenges and Future Perspectives.Journal of clinical medicine · 2021Review
- Challenges in modeling EWS-FLI1-driven transgenic mouse model for Ewing sarcoma.American journal of translational research · 2021Review
- Sarcoma treatment in the era of molecular medicine.EMBO molecular medicine · 2020Review
- Genetic Engineering of Zebrafish in Cancer Research.Cancers · 2020Review
- Zebrafish In Vivo Models of Cancer and Metastasis.Cold Spring Harbor perspectives in medicine · 2020Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ewing's sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing's sarcoma family tumors (ESFTs), which include peripheral primitive neuroectodermal tumors (PNETs), are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing's sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing's sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing's sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.
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