ArticleOncogene2021
Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Modelling EWS::FLI1 protein fluctuations reveal determinants of tumor plasticity in Ewing sarcoma.EMBO molecular medicine · 2026Article
- DCMiC: a double-cylinder micro-chamber platform for high-throughput drug screening and modeling of microenvironmental resistance in Ewing sarcoma.Lab on a chip · 2026Article
- Combinatorial functionomics identifies HDAC6-dependent molecular vulnerability of radioresistant head and neck cancer.Experimental hematology & oncology · 2025Article
- A novel histone acetylation-associated gene signature with prognostic value in Ewing sarcoma.Discover oncology · 2024Article
- Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma.Molecular cancer · 2024Article
- BML-281 promotes neuronal differentiation by modulating Wnt/CaMolecular and cellular biochemistry · 2024Article
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 2022Review
- Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-β via Smad3 acetylation.Nature communications · 2022Article
- Ewing Sarcoma Meets Epigenetics, Immunology and Nanomedicine: Moving Forward into Novel Therapeutic Strategies.Cancers · 2022Review
- Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022Review
- 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
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and tumor progression processes has been described in-depth, little is known about the regulation of chimeric fusion-gene expression. Here, we demonstrate that the active nuclear HDAC6 in EWS modulates the acetylation status of specificity protein 1 (SP1), consequently regulating the SP1/P300 activator complex binding to EWSR1 and EWSR1-FLI1 promoters. Selective inhibition of HDAC6 impairs binding of the activator complex SP1/P300, thereby inducing EWSR1-FLI1 downregulation and significantly reducing its oncogenic functions. In addition, sensitivity of EWS cell lines to HDAC6 inhibition is higher than other tumor or non-tumor cell lines. High expression of HDAC6 in primary EWS tumor samples from patients correlates with a poor prognosis in two independent series accounting 279 patients. Notably, a combination treatment of a selective HDAC6 and doxorubicin (a DNA damage agent used as a standard therapy of EWS patients) dramatically inhibits tumor growth in two EWS murine xenograft models. These results could lead to suitable and promising therapeutic alternatives for patients with EWS.
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