ArticleOncotarget2017
Tumorigenicity of Ewing sarcoma is critically dependent on the trithorax proteins MLL1 and menin.
Article in Oncotarget, 2017. 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, 38 citations in OpenAlex.
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Menin: from molecular insights to clinical impact.Epigenomics · 2025Review
- Sarcomas arising in MEN1 patients: demonstrating LOH of the MEN1 locus and loss of menin expression.Familial cancer · 2024Article
- Menin in Cancer.Genes · 2024Review
- Pharmacological targeting of the cancer epigenome.Nature cancer · 2024Review
- Article
- Dependency of B-Cell Acute Lymphoblastic Leukemia and Multiple Myeloma Cell Lines on MEN1 Extends beyond MEN1-KMT2A Interaction.International journal of molecular sciences · 2023Article
- Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.Cell reports · 2022Article
- 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
- Article
- 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
- Amino acid metabolism in primary bone sarcomas.Frontiers in oncology · 2022Review
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
- Review
- EWS-FLI1 and Menin Converge to Regulate ATF4 Activity in Ewing Sarcoma.Molecular cancer research : MCR · 2021Article
- Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium.Pediatric blood & cancer · 2020Article
- Article
- Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma.Pediatric blood & cancer · 2019Article
- Gliosarcoma: distinct molecular pathways and genomic alterations identified by DNA copy number/SNP microarray analysis.Journal of neuro-oncology · 2019Article
- Anatomic Origin of Osteochondrogenic Progenitors Impacts Sensitivity to EWS-FLI1-Induced Transformation.Cancers · 2019Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Developmental transcription programs are epigenetically regulated by the competing actions of polycomb and trithorax (TrxG) protein complexes, which repress and activate genes, respectively. Ewing sarcoma is a developmental tumor that is associated with widespread de-regulation of developmental transcription programs, including HOX programs. Posterior HOXD genes are abnormally over-expressed by Ewing sarcoma and HOXD13, in particular, contributes to the tumorigenic phenotype. In MLL1 fusion-driven leukemia, aberrant activation of HOXA genes is epigenetically mediated by the TrxG complex and HOXA gene expression and leukemogenesis are critically dependent on the protein-protein interaction between the TrxG proteins MLL1 and menin. Based on these data, we investigated whether posterior HOXD gene activation and Ewing sarcoma tumorigenicity are similarly mediated by and dependent on MLL1 and/or menin. Our findings demonstrate that Ewing sarcomas express high levels of both MLL1 and menin and that continued expression of both proteins is required for maintenance of tumorigenicity. In addition, exposure of Ewing sarcoma cells to MI-503, an inhibitor of the MLL1-menin protein-protein interaction developed for MLL1-fusion driven leukemia, leads to loss of tumorigenicity and down-regulated expression of the posterior HOXD gene cluster. Together these data demonstrate an essential role for MLL1 and menin in mediating tumor maintenance and posterior HOXD gene activation in Ewing sarcoma. A critical dependency of these tumors on the MLL1-menin interaction presents a potentially novel therapeutic target.
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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.