ArticlePloS one2008
EWS/FLI mediates transcriptional repression via NKX2.2 during oncogenic transformation in Ewing's sarcoma.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 151 citations in OpenAlex.
- A phase II trial of panobinostat in patients with advanced pretreated soft tissue sarcoma. A study from the French Sarcoma Group.British journal of cancer · 2013Trial
- Article
- Modelling EWS::FLI1 protein fluctuations reveal determinants of tumor plasticity in Ewing sarcoma.EMBO molecular medicine · 2026Article
- Identification of circRNA/lncRNA-miRNA-Transcription Factor-mRNA Networks to Identify Potential Biomarkers in Response to Neoadjuvant Therapy for Breast Cancer.Breast cancer (Dove Medical Press) · 2026Article
- Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.Molecular oncology · 2025Article
- Plasma DNA Methylation-Based Biomarkers for MPNST Detection in Patients With Neurofibromatosis Type 1.Molecular carcinogenesis · 2025Article
- Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity.The American journal of pathology · 2023Article
- EWS/FLI1 Characterization, Activation, Repression, Target Genes and Therapeutic Opportunities in Ewing Sarcoma.International journal of molecular sciences · 2023Review
- CRISPR-Cas9 knockout screening identifies KIAA1429 as an essential gene in Ewing sarcoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- Inferring cell-type-specific causal gene regulatory networks during human neurogenesis.Genome biology · 2023Article
- Regulation of EWSR1-FLI1 Function by Post-Transcriptional and Post-Translational Modifications.Cancers · 2023Review
- Targeting STEAP1 as an anticancer strategy.Frontiers in oncology · 2023Review
- Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.Cell reports · 2022Article
- Ewing sarcoma of the ileum with wide multiorgan metastases: A case report and review of literature.World journal of gastrointestinal oncology · 2022Article
- Epigenetic and Transcriptional Signaling in Ewing Sarcoma-Disease Etiology and Therapeutic Opportunities.Biomedicines · 2022Review
- The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review.Frontiers in oncology · 2022Review
- AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing's sarcoma cells.PloS one · 2022Article
- Article
- Cancer biology functional genomics: From small RNAs to big dreams.Molecular carcinogenesis · 2020Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
EWS/FLI is a master regulator of Ewing's sarcoma formation. Gene expression studies in A673 Ewing's sarcoma cells have demonstrated that EWS/FLI downregulates more genes than it upregulates, suggesting that EWS/FLI, and/or its targets, function as transcriptional repressors. One critical EWS/FLI target, NKX2.2, is a transcription factor that contains both transcriptional activation and transcriptional repression domains, raising the possibility that it mediates portions of the EWS/FLI transcriptional signature. We now report that microarray analysis demonstrated that the transcriptional profile of NKX2.2 consists solely of downregulated genes, and overlaps with the EWS/FLI downregulated signature, suggesting that NKX2.2 mediates oncogenic transformation via transcriptional repression. Structure-function analysis revealed that the DNA binding and repressor domains in NKX2.2 are required for oncogenesis in Ewing's sarcoma cells, while the transcriptional activation domain is completely dispensable. Furthermore, blockade of TLE or HDAC function, two protein families thought to mediate the repressive function of NKX2.2, inhibited the transformed phenotype and reversed the NKX2.2 transcriptional profile in Ewing's sarcoma cells. Whole genome localization studies (ChIP-chip) revealed that a significant portion of the NKX2.2-repressed gene expression signature was directly mediated by NKX2.2 binding. These data demonstrate that the transcriptional repressive function of NKX2.2 is necessary, and sufficient, for the oncogenic phenotype of Ewing's sarcoma, and suggest a therapeutic approach to this disease.
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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.