ArticleGenome research2013
Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer.
Article in Genome research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Advances in sequencing and omics studies in prostate cancer: unveiling molecular pathogenesis and clinical applications.Frontiers in oncology · 2024Pooled it
- Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial.Nature medicine · 2026Trial
- A Practical Compass to Biological Digital Resources and Omics Integration in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Mithramycin alters EWS::FLI1 DNA binding and RNA polymerase II processivity to inhibit nascent transcription.Nature communications · 2026Article
- Modelling EWS::FLI1 protein fluctuations reveal determinants of tumor plasticity in Ewing sarcoma.EMBO molecular medicine · 2026Article
- EWS::FLI1 expression in human embryonic mesenchymal stem cells leads to transcriptional reprograming, defective DNA damage repair and Ewing sarcoma.Nature communications · 2025Article
- EWS::FLI1-DHX9 interaction promotes Ewing sarcoma sensitivity to DNA topoisomerase 1 poisons by altering R-loop metabolism.Oncogene · 2025Article
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- Oncogenic ETS fusions promote DNA damage and proinflammatory responses via pericentromeric RNAs in extracellular vesicles.The Journal of clinical investigation · 2024Article
- MicroRNA-495: a therapeutic and diagnostic tumor marker.Journal of molecular histology · 2023Review
- SilenceREIN: seeking silencers on anchors of chromatin loops by deep graph neural networks.Briefings in bioinformatics · 2023Article
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1-EEF1A1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Long non-coding RNAs involved in retinoblastoma.Journal of cancer research and clinical oncology · 2023Review
- Exosome-Derived microRNA: Implications in Melanoma Progression, Diagnosis and Treatment.Cancers · 2022Review
- Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.Cell reports · 2022Article
- Downregulation of hsa_circ_0000885 suppressed osteosarcoma metastasis and progression via regulating E2F3 expression and sponging miR-16-5p.Regenerative therapy · 2022Article
- Neomorphic DNA-binding enables tumor-specific therapeutic gene expression in fusion-addicted childhood sarcoma.Molecular cancer · 2022Article
- Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Deregulated E2F transcription factor activity occurs in the vast majority of human tumors and has been solidly implicated in disturbances of cell cycle control, proliferation, and apoptosis. Aberrant E2F regulatory activity is often caused by impairment of control through pRB function, but little is known about the interplay of other oncoproteins with E2F. Here we show that ETS transcription factor fusions resulting from disease driving rearrangements in Ewing sarcoma (ES) and prostate cancer (PC) are one such class of oncoproteins. We performed an integrative study of genome-wide DNA-binding and transcription data in EWSR1/FLI1 expressing ES and TMPRSS2/ERG containing PC cells. Supported by promoter activity and mutation analyses, we demonstrate that a large fraction of E2F3 target genes are synergistically coregulated by these aberrant ETS proteins. We propose that the oncogenic effect of ETS fusion oncoproteins is in part mediated by the disruptive effect of the E2F-ETS interaction on cell cycle control. Additionally, a detailed analysis of the regulatory targets of the characteristic EWSR1/FLI1 fusion in ES identifies two functionally distinct gene sets. While synergistic regulation in concert with E2F in the promoter of target genes has a generally activating effect, EWSR1/FLI1 binding independent of E2F3 is predominantly associated with repressed differentiation genes. Thus, EWSR1/FLI1 appears to promote oncogenesis by simultaneously promoting cell proliferation and perturbing differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.