ArticleThe Journal of clinical investigation2021
ETV4 and ETV5 drive synovial sarcoma through cell cycle and DUX4 embryonic pathway control.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- FGFR1 signaling in rheumatoid arthritis: Mechanisms of bone destruction and therapeutic targeting (Review).International journal of molecular medicine · 2026Review
- Gut-bone axis in rheumatoid arthritis: microbiota-driven barrier dysfunction, immune crosstalk, and therapeutic strategies.Antonie van Leeuwenhoek · 2026Review
- Molecular and epigenetic oncogenesis in synovial sarcoma: implications for cancer biology, diagnosis and treatment.Oncogene · 2025Review
- Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis.The EMBO journal · 2025Article
- Upregulation of POLE and proficient DNA repair are features of CIC::DUX4 sarcomas.NPJ precision oncology · 2025Article
- Cancer and benign tumors in myotonic dystrophy, facioscapulohumeral muscular dystrophy, and oculopharyngeal muscular dystrophy: a 23-year, single-center, retrospective study.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Article
- Identification of ETV5 as a prognostic marker related to epigenetic modification in pan-cancer and facilitates tumor progression in hepatocellular carcinoma.Scientific reports · 2024Article
- Genetic and Molecular Heterogeneity of Synovial Sarcoma and Associated Challenges in Therapy.Cells · 2024Review
- Review
- Biological and therapeutic insights from animal modeling of fusion-driven pediatric soft tissue sarcomas.Disease models & mechanisms · 2024Review
- FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions.Nature reviews. Clinical oncology · 2024Review
- ETV5 regulates proliferation and cell cycle genes in the INS-1 (832/13) cell line independently of the concentration of secreted insulin.FEBS open bio · 2023Article
- 2-Bromopalmitate inhibits malignant behaviors of HPSCC cells by hindering the membrane location of Ras protein.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers.Oncogene · 2023Review
- ETV4 Mediated Tumor-Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function.Journal of biomedical science · 2023Review
- Article
- Review
- Ccn2a-FGFR1-SHH signaling is necessary for intervertebral disc homeostasis and regeneration in adult zebrafish.Development (Cambridge, England) · 2023Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Synovial sarcoma is an aggressive malignancy with no effective treatments for patients with metastasis. The synovial sarcoma fusion SS18-SSX, which recruits the SWI/SNF-BAF chromatin remodeling and polycomb repressive complexes, results in epigenetic activation of FGF receptor (FGFR) signaling. In genetic FGFR-knockout models, culture, and xenograft synovial sarcoma models treated with the FGFR inhibitor BGJ398, we show that FGFR1, FGFR2, and FGFR3 were crucial for tumor growth. Transcriptome analyses of BGJ398-treated cells and histological and expression analyses of mouse and human synovial sarcoma tumors revealed prevalent expression of two ETS factors and FGFR targets, ETV4 and ETV5. We further demonstrate that ETV4 and ETV5 acted as drivers of synovial sarcoma growth, most likely through control of the cell cycle. Upon ETV4 and ETV5 knockdown, we observed a striking upregulation of DUX4 and its transcriptional targets that activate the zygotic genome and drive the atrophy program in facioscapulohumeral dystrophy patients. In addition to demonstrating the importance of inhibiting all three FGFRs, the current findings reveal potential nodes of attack for the cancer with the discovery of ETV4 and ETV5 as appropriate biomarkers and molecular targets, and activation of the embryonic DUX4 pathway as a promising approach to block synovial sarcoma tumors.
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