ArticleNucleic acids research2020
EWS-FLI1 regulates and cooperates with core regulatory circuitry in Ewing sarcoma.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- Harnessing MDM2-Mediated Targeted Degradation of Transcriptional and Epigenetic Machinery to Disrupt Oncogenic Addictions in Pediatric Sarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Non-Canonical Core Transcriptional Regulatory Circuit Orchestrates Chromatin Reprogramming to Drive Osimertinib Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Super-enhancer-driven TCF4 orchestrates neuroblastoma metastasis by sphingolipid-dependent membrane remodeling and ITGB1-FAK activation.Neuro-oncology · 2026Article
- Reprogramming lipid metabolism in pediatric cancers.Oncogenesis · 2026Review
- Super-Enhancer-Driven SOX4/SMAD3 Mediate Membrane Remodeling by Regulating Phospholipid Metabolism to Accelerate Leukemia Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Evolutionarily Conserved TPM1 Super-Enhancer Drives Skeletal Muscle Regeneration via Mechanotransduction Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modelling EWS::FLI1 protein fluctuations reveal determinants of tumor plasticity in Ewing sarcoma.EMBO molecular medicine · 2026Article
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- The hegemonic EWSR1::ETS oncoprotein overrules core regulatory circuitry principles in Ewing sarcoma.NPJ precision oncology · 2025Article
- A Super-Enhancer-Driven Transcriptional Regulatory Circuit Underlying Abiraterone Resistance in Castration-Resistant Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Interplay and cooperation between GLI2 and master transcription factors promote progression of esophageal squamous cell carcinoma.American journal of human genetics · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Identifying Lipid Metabolism-Related Therapeutic Targets and Diagnostic Markers for Lung Adenocarcinoma by Mendelian Randomization and Machine Learning Analysis.Thoracic cancer · 2025Article
- Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research.Biomedicines · 2024Review
- ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3.Molecular cancer research : MCR · 2024Article
- Unlocking epigenetics for precision treatment of Ewing's sarcoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma.Acta pharmaceutica Sinica. B · 2024Article
- Contribution ofmedRxiv : the preprint server for health sciences · 2024Article
- Metabolic reprogramming directed by super-enhancers in tumors: An emerging landscape.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Core regulatory circuitry (CRC)-dependent transcriptional network is critical for developmental tumors in children and adolescents carrying few gene mutations. However, whether and how CRC contributes to transcription regulation in Ewing sarcoma is unknown. Here, we identify and functionally validate a CRC 'trio' constituted by three transcription factors (TFs): KLF15, TCF4 and NKX2-2, in Ewing sarcoma cells. Epigenomic analyses demonstrate that EWS-FLI1, the primary fusion driver for this cancer, directly establishes super-enhancers of each of these three TFs to activate their transcription. In turn, KLF15, TCF4 and NKX2-2 co-bind to their own and each other's super-enhancers and promoters, forming an inter-connected auto-regulatory loop. Functionally, CRC factors contribute significantly to cell proliferation of Ewing sarcoma both in vitro and in vivo. Mechanistically, CRC factors exhibit prominent capacity of co-regulating the epigenome in cooperation with EWS-FLI1, occupying 77.2% of promoters and 55.6% of enhancers genome-wide. Downstream, CRC TFs coordinately regulate gene expression networks in Ewing sarcoma, controlling important signaling pathways for cancer, such as lipid metabolism pathway, PI3K/AKT and MAPK signaling pathways. Together, molecular characterization of the oncogenic CRC model advances our understanding of the biology of Ewing sarcoma. Moreover, CRC-downstream genes and signaling pathways may contain potential therapeutic targets for this malignancy.
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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.