ArticleOncogene2010
EGR1 reactivation by histone deacetylase inhibitors promotes synovial sarcoma cell death through the PTEN tumor suppressor.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 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
- Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis.The EMBO journal · 2025Article
- Combination of HDAC and FYN inhibitors in synovial sarcoma treatment.Frontiers in cell and developmental biology · 2024Article
- HEY1-NCOA2 expression modulates chondrogenic differentiation and induces mesenchymal chondrosarcoma in mice.JCI insight · 2023Article
- Review
- EGFR is a master switch between immunosuppressive and immunoactive tumor microenvironment in inflammatory breast cancer.Science advances · 2022Article
- Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Identification of Tumor Microenvironment-Related Prognostic Genes in Sarcoma.Frontiers in genetics · 2021Article
- Ring finger protein 2 promotes colorectal cancer progression by suppressing early growth response 1.Aging · 2020Article
- The Mechanisms Underlying PTEN Loss in Human Tumors Suggest Potential Therapeutic Opportunities.Biomolecules · 2019Review
- The PTEN Tumor Suppressor Gene in Soft Tissue Sarcoma.Cancers · 2019Review
- HDAC2 Regulates Site-Specific Acetylation of MDM2 and Its Ubiquitination Signaling in Tumor Suppression.iScience · 2019Article
- Podocyte histone deacetylase activity regulates murine and human glomerular diseases.The Journal of clinical investigation · 2019Article
- Revisiting the Clinical and Biologic Relevance of Partial PTEN Loss in Melanoma.The Journal of investigative dermatology · 2019Article
- Histone deacetylase inhibitor ITF2357 leads to apoptosis and enhances doxorubicin cytotoxicity in preclinical models of human sarcoma.Oncogenesis · 2018Article
- Histone deacetylase inhibitors vorinostat and panobinostat induce G1 cell cycle arrest and apoptosis in multidrug resistant sarcoma cell lines.Oncotarget · 2017Article
- Therapeutic applications of histone deacetylase inhibitors in sarcoma.Cancer treatment reviews · 2017Review
- Normalization of Hepatic Homeostasis in theThe Journal of biological chemistry · 2017Article
- Advances in sarcoma diagnostics and treatment.Oncotarget · 2017Review
- HDAC and Proteasome Inhibitors Synergize to Activate Pro-Apoptotic Factors in Synovial Sarcoma.PloS one · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synovial sarcoma is a high-grade soft tissue malignancy, for which current cytotoxic chemotherapies provide limited benefit. Although histone deacetylase (HDAC) inhibitors are known to suppress synovial sarcoma in vitro and in vivo, the exact mechanism is not clear. In this study, we report a central role of the transcription factor, early growth response-1 (EGR1), in the regulation of HDAC inhibitor-induced apoptotic cell death in synovial sarcoma. The SS18-SSX oncoprotein, characteristic of synovial sarcoma, maintains EGR1 expression at low levels, whereas it is significantly increased after HDAC inhibitor treatment. On the contrary, EGR1 knockdown leads to a decrease in HDAC inhibitor-induced apoptosis. Moreover, we find that under these conditions phosphatase and tensin homolog deleted in chromosome 10 (PTEN) is upregulated and this occurs through direct binding of EGR1 to an element upstream of the PTEN promoter. Using a combination of gain- and loss-of-function approaches, we show that EGR1 modulation of PTEN contributes to HDAC inhibitor-induced apoptosis in synovial sarcoma. Finally, restoration of EGR1 or PTEN expression is sufficient to induce synovial sarcoma cell death. Taken together, our findings indicate that SS18-SSX-mediated attenuation of an EGR1-PTEN network regulates synovial sarcoma cell survival, and that HDAC inhibitor-mediated apoptosis operates at least in part through reactivation of this pathway.
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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.