ArticleMolecular and cellular biology2003
Alteration of mesodermal cell differentiation by EWS/FLI-1, the oncogene implicated in Ewing's sarcoma.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 69 citations in OpenAlex.
- Druggable upregulated proteins in EWS-FLI-driven Ewing sarcoma as emerging new therapeutic targets.American journal of translational research · 2025Review
- ETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation.Nature cell biology · 2023Article
- Epigenetic and Transcriptional Signaling in Ewing Sarcoma-Disease Etiology and Therapeutic Opportunities.Biomedicines · 2022Review
- Inhibitor of DNA binding 2 (ID2) regulates the expression of developmental genes and tumorigenesis in ewing sarcoma.Oncogene · 2022Article
- Oncogenes, Proto-Oncogenes, and Lineage Restriction of Cancer Stem Cells.International journal of molecular sciences · 2021Review
- MYB oncoproteins: emerging players and potential therapeutic targets in human cancer.Oncogenesis · 2021Review
- Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases.Cell stress · 2020Review
- Acquisition of an oncogenic fusion protein is sufficient to globally alter the landscape of miRNA expression to inhibit myogenic differentiation.Oncotarget · 2017Article
- IRE1a constitutes a negative feedback loop with BMP2 and acts as a novel mediator in modulating osteogenic differentiation.Cell death & disease · 2014Article
- Salient features of mesenchymal stem cells-implications for Ewing sarcoma modeling.Frontiers in oncology · 2013Article
- Functions of heterogeneous nuclear ribonucleoproteins in stem cell potency and differentiation.BioMed research international · 2013Review
- Molecular pathogenesis of Ewing sarcoma: new therapeutic and transcriptional targets.Annual review of pathology · 2012Review
- CD99/MIC2 Constitutes a Differentiation Antigen of a Human Osteoblast Cell Line.World journal of oncology · 2011Article
- Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening.Journal of the National Cancer Institute · 2011Article
- The Ewing's sarcoma fusion protein, EWS-FLI, binds Runx2 and blocks osteoblast differentiation.Journal of cellular biochemistry · 2010Article
- Pathology of Ewing's sarcoma/PNET: Current opinion and emerging concepts.Indian journal of orthopaedics · 2010Article
- EWS/ETS proteins promote expression and regulate function of the homeodomain transcription factor BRN3A.Oncogene · 2010Article
- The TET family of proteins: functions and roles in disease.Journal of molecular cell biology · 2009Review
- EWS-FLI1 induces developmental abnormalities and accelerates sarcoma formation in a transgenic mouse model.Cancer research · 2008Article
- Neural differentiation arrest in embryonal carcinoma cells with forced expression of EWS-FLI1.Journal of neuro-oncology · 2008Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The chimeric fusion gene EWS/FLI-1 is detected in most cases of Ewing's sarcoma (ES), the second most common malignant bone tumor of childhood. Although 80% of ES tumors develop in skeletal sites, the remainder can arise in almost any soft tissue location. The lineage of the cell developing the EWS/FLI-1 gene fusion has not been fully characterized but is generally considered to be of either mesenchymal or neural crest origin. To study this oncogene in a conceptually relevant target cell, EWS/FLI-1 was introduced into the murine cell line C2C12, a myoblast cell line capable of differentiation into muscle, bone, or fat. In this cellular context, EWS/FLI-1 profoundly inhibited the myogenic differentiation program. The block in C2C12 myogenic differentiation required the nuclear localization and DNA-binding functions of EWS/FLI-1 and was mediated by transcriptional and posttranscriptional suppression of the myogenic transcription factors MyoD and myogenin. Interestingly, C2C12-EWS/FLI-1 cells constitutively expressed alkaline phosphatase, a bone lineage marker, and were alkaline phosphatase positive by histochemistry but showed no other evidence of bone lineage commitment. Consistent with recent findings in human ES tumor cell lines, C2C12-EWS/FLI-1 cells constitutively expressed cyclin D1 and demonstrated decreased expression of the cell cycle regulator p21(cip1), even under differentiation conditions and at confluent density. This C2C12-EWS/FLI-1 cell model may assist in the identification of novel differentially expressed genes relevant to ES and provide further insight into the cell(s) of origin developing ES-associated genetic fusions.
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