ArticleProceedings of the National Academy of Sciences of the United States of America2016
HIFI-α activation underlies a functional switch in the paradoxical role of Ezh2/PRC2 in breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 90 citations in OpenAlex.
- Article
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- The Pro-Metastatic Roles of ROS.Antioxidants (Basel, Switzerland) · 2026Review
- Noncanonical association of EZH2 with E2F1 promotes tumor proliferation through chromatin remodeling.Experimental & molecular medicine · 2025Article
- Investigation of the clinical significance of the expression of immunohistochemical biomarkers Enhancer of zeste homolog 2 and Forkhead box M1 in localized prostate cancer tissue: A Greek retrospective study.Asian journal of urology · 2025Article
- Role of epigenetics in paediatric cancer pathogenesis & drug resistance.British journal of cancer · 2025Review
- Myocardial infarction activates the 9p21.3 orthologous locus expression, but its absence does not alter cardiac pathophysiology in ischemia.Physiological reports · 2025Article
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- Exploring oncogenic roles and clinical significance of EZH2: focus on non-canonical activities.Therapeutic advances in medical oncology · 2025Review
- Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review.Life (Basel, Switzerland) · 2024Review
- Elucidation of Dysregulated Pathways Associated With Hypoxia in Oestrogen Receptor-Negative Breast Cancer.Cancer medicine · 2024Article
- Multi-output prediction of dose-response curves enables drug repositioning and biomarker discovery.NPJ precision oncology · 2024Article
- EZH2 PROTACs target EZH2- and FOXM1-associated oncogenic nodes, suppressing breast cancer cell growth.Oncogene · 2024Article
- Hypoxia makes EZH2 inhibitor not easy-advances of crosstalk between HIF and EZH2.Life metabolism · 2024Article
- Hypoxia-activated XBP1s recruits HDAC2-EZH2 to engage epigenetic suppression of ΔNp63α expression and promote breast cancer metastasis independent of HIF1α.Cell death and differentiation · 2024Article
- Role of EZH2-mediated epigenetic modification on vascular smooth muscle in cardiovascular diseases: A mini-review.Frontiers in pharmacology · 2024Review
- Tazemetostat decreases β-catenin and CD13 protein expression in HEPG-2 and Hepatitis B virus-transfected HEPG-2 with decreased cell viability.Clinical epigenetics · 2023Article
- Utilizing network pharmacology and experimental validation to explore the potential molecular mechanisms of rawJournal of gastrointestinal oncology · 2023Article
- Role of succinate in airway epithelial cell regulation following traumatic lung injury.JCI insight · 2023Article
- FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the established oncogenic function of Polycomb repressive complex 2 (PRC2) in human cancers, its role as a tumor suppressor is also evident; however, the mechanism underlying the regulation of the paradoxical functions of PRC2 in tumorigenesis is poorly understood. Here we show that hypoxia-inducible factor 1, α-subunit (HIFI-α) is a crucial modulator of PRC2 and enhancer of zeste 2 (EZH2) function in breast cancer. Interrogating the genomic expression of breast cancer indicates high HIF1A activity correlated with high EZH2 expression but low PRC2 activity in triple-negative breast cancer compared with other cancer subtypes. In the absence of HIFIA activation, PRC2 represses the expression of matrix metalloproteinase genes (MMPs) and invasion, whereas a discrete Ezh2 complexed with Forkhead box M1 (FoxM1) acts to promote the expression of MMPs. HIF1-α induction upon hypoxia results in PRC2 inactivation by selective suppression of the expression of suppressor of zeste 12 protein homolog (SUZ12) and embryonic ectoderm development (EED), leading to a functional switch toward Ezh2/FoxM1-dependent induction of the expression of MMPs and invasion. Our study suggests a tumor-suppressive function of PRC2, which is restricted by HIF1-α, and an oncogenic function of Ezh2, which cooperates with FoxM1 to promote invasion in triple-negative breast cancer.
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