ArticleNature communications2016
Epigenetic re-expression of HIF-2α suppresses soft tissue sarcoma growth.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?Frontiers in oncology · 2021Pooled it
- A tailored in vivo CRISPR screen identifies BAP1 as a potent tumor suppressor of sarcoma.JCI insight · 2026Article
- Role of hypoxia-inducible factor - 1 alpha on the progression of cervical intraepithelial neoplasia and cervical cancer: a narrative review.Frontiers in oncology · 2026Review
- High-throughput screening identifies the activity of histone deacetylase inhibitors in patient-derived models of soft tissue sarcoma.Cancer biology & therapy · 2025Article
- HIF2α negatively regulates MYCN protein levels and promotes a low-risk noradrenergic phenotype in neuroblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PRMT5 regulates alternative splicing of TCF3 under hypoxia to promote EMT and invasion in breast cancer.PLoS biology · 2025Article
- Aging impairs CD8 T cell responses in adoptive T-cell therapy against solid tumors.Frontiers in immunology · 2025Article
- Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.Life (Basel, Switzerland) · 2023Review
- EPAS1/HIF-2α Acts as an Unanticipated Tumor-Suppressive Role in Papillary Thyroid Carcinoma.International journal of general medicine · 2023Article
- Current research and management of undifferentiated pleomorphic sarcoma/myofibrosarcoma.Frontiers in genetics · 2023Review
- Updated perspective of EPAS1 and the role in pulmonary hypertension.Frontiers in cell and developmental biology · 2023Review
- Bioinformatics Analysis Identifies EPAS1 as a Novel Prognostic Marker Correlated with Immune Infiltration in Acute Myeloid Leukemia.Disease markers · 2023Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Crosstalk among mJournal of hematology & oncology · 2022Review
- FG-4592 protects the intestine from irradiation-induced injury by targeting the TLR4 signaling pathway.Stem cell research & therapy · 2022Article
- Vitamin D and Hypoxia: Points of Interplay in Cancer.Cancers · 2022Review
- Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy.Cancers · 2022Review
- Immunological and prognostic significance of novel ferroptosis-related genes in soft tissue sarcoma.PloS one · 2022Article
- Epigenetic Regulation During Hypoxia and Its Implications in Cancer.Sub-cellular biochemistry · 2022Article
- Epigenetics of Cutaneous Sarcoma.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In soft tissue sarcomas (STS), low intratumoural O2 (hypoxia) is a poor prognostic indicator. HIF-1α mediates key transcriptional responses to hypoxia, and promotes STS metastasis; however, the role of the related HIF-2α protein is unknown. Surprisingly, here we show that HIF-2α inhibits high-grade STS cell growth in vivo, as loss of HIF-2α promotes sarcoma proliferation and increases calcium and mTORC1 signalling in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. We find that most human STS have lower levels of EPAS1 (the gene encoding HIF-2α) expression relative to normal tissue. Many cancers, including STS, contain altered epigenetics, and our findings define an epigenetic mechanism whereby EPAS1 is silenced during sarcoma progression. The clinically approved HDAC inhibitor Vorinostat specifically increases HIF-2α, but not HIF-1α, accumulation in multiple STS subtypes. Vorinostat inhibits STS tumour growth, an effect ameliorated by HIF-2α deletion, implicating HIF-2α as a biomarker for Vorinostat efficacy in STS.
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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.