ArticleCancer research2010
Hypoxia modulates EWS-FLI1 transcriptional signature and enhances the malignant properties of Ewing's sarcoma cells in vitro.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Clinicopathological and prognostic value of hypoxia-inducible factor-1α in patients with bone tumor: a systematic review and meta-analysis.Journal of orthopaedic surgery and research · 2019Pooled it
- Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma.Science advances · 2026Article
- Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- Regulation of EWSR1-FLI1 Function by Post-Transcriptional and Post-Translational Modifications.Cancers · 2023Review
- EWS::FLI1 and HOXD13 Control Tumor Cell Plasticity in Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Regulation of Metastasis in Ewing Sarcoma.Cancers · 2022Review
- Oncofusion-driven de novo enhancer assembly promotes malignancy in Ewing sarcoma via aberrant expression of the stereociliary protein LOXHD1.Cell reports · 2022Article
- Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma.Nature communications · 2022Article
- 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
- A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma.Frontiers in genetics · 2022Article
- The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites.Nature metabolism · 2021Article
- Metabolic landscapes in sarcomas.Journal of hematology & oncology · 2021Review
- PDX-Derived Ewing's Sarcoma Cells Retain High Viability and Disease Phenotype in Alginate Encapsulated Spheroid Cultures.Cancers · 2021Article
- Hypoxia and its therapeutic possibilities in paediatric cancers.British journal of cancer · 2021Review
- Imatinib revives the therapeutic potential of metformin on ewing sarcoma by attenuating tumor hypoxic response and inhibiting convergent signaling pathways.Cancer letters · 2020Article
- The NOTCH1-dependent HIF1α/VGLL4/IRF2BP2 oxygen sensing pathway triggers erythropoiesis terminal differentiation.Redox biology · 2020Article
- The Role of C-X-C Chemokine Receptor Type 4 (CXCR4) in Cell Adherence and Spheroid Formation of Human Ewing's Sarcoma Cells under Simulated Microgravity.International journal of molecular sciences · 2019Article
- New Insights about the Wnt/β-Catenin Signaling Pathway in Primary Bone Tumors and Their Microenvironment: A Promising Target to Develop Therapeutic Strategies?International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypoxia is an important condition in the tumor cell microenvironment and approximately 1% to 1.5% of the genome is transcriptionally responsive to hypoxia with hypoxia-inducible factor-1 (HIF-1) as a major mediator of transcriptional activation. Tumor hypoxia is associated with a more aggressive phenotype of many cancers in adults, but data on pediatric tumors are scarce. Because, by immunohistochemistry, HIF-1alpha expression was readily detectable in 18 of 28 primary Ewing's sarcoma family tumors (ESFT), a group of highly malignant bone-associated tumors in children and young adults, we studied the effect of hypoxia on ESFT cell lines in vitro. Intriguingly, we found that EWS-FLI1 protein expression, which characterizes ESFT, is upregulated by hypoxia in a HIF-1alpha-dependent manner. Hypoxia modulated the EWS-FLI1 transcriptional signature relative to normoxic conditions. Both synergistic as well as antagonistic transcriptional effects of EWS-FLI1 and of hypoxia were observed. Consistent with alterations in the expression of metastasis-related genes, hypoxia stimulated the invasiveness and soft agar colony formation of ESFT cells in vitro. Our data represent the first transcriptome analysis of hypoxic ESFT cells and identify hypoxia as an important microenvironmental factor modulating EWS-FLI1 expression and target gene activity with far-reaching consequences for the malignant properties of ESFT.
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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.