ArticleCancer research2011
Histone methyltransferase EZH2 induces Akt-dependent genomic instability and BRCA1 inhibition in breast cancer.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 112 citations in OpenAlex.
- EZH2 as regulator of stemness signature and driver of esophageal squamous cell carcinomas.Scientific reports · 2026Article
- SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting racial disparities in breast cancer: mechanistic insights and therapeutic potential of African medicinal plants.Medical oncology (Northwood, London, England) · 2025Review
- Review
- Expression of EZH2 and Fatty Acid Synthase in Breast Tissues From Healthy Women With Breast Cancer Risk Factors.Applied immunohistochemistry & molecular morphology : AIMM · 2025Article
- H3K27me3-mediated epigenetic regulation in pluripotency maintenance and lineage differentiation.Cell insight · 2024Review
- Epigenetic activation of SOX11 is associated with recurrence and progression of ductal carcinoma in situ to invasive breast cancer.British journal of cancer · 2024Article
- EZH2-Myc Hallmark in Oncovirus/Cytomegalovirus Infections and Cytomegalovirus' Resemblance to Oncoviruses.Cells · 2024Review
- scGRN: a comprehensive single-cell gene regulatory network platform of human and mouse.Nucleic acids research · 2024Article
- Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.Journal of translational medicine · 2024Review
- Unveiling the Mechanisms and Therapeutic Effects of Xiaoyao Sanjie Decoction in Triple-Negative Breast Cancer: A Network Pharmacology and Experimental Validation Approach.Drug design, development and therapy · 2024Article
- A hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis.JCI insight · 2023Article
- Dissecting and targeting noncanonical functions of EZH2 in multiple myeloma via an EZH2 degrader.Oncogene · 2023Article
- Polycomb Repressive Complex 2 in Oncology.Cancer treatment and research · 2023Article
- EZH2 T367 phosphorylation activates p38 signaling through lysine methylation to promote breast cancer progression.iScience · 2022Article
- Polyploid giant cancer cells, EZH2 and Myc upregulation in mammary epithelial cells infected with high-risk human cytomegalovirus.EBioMedicine · 2022Article
- Pharmacologic Induction of BRCAness inCancers · 2022Review
- EZH2 engages TGFβ signaling to promote breast cancer bone metastasis via integrin β1-FAK activation.Nature communications · 2022Article
- Methylation-dependent and -independent roles of EZH2 synergize in CDCA8 activation in prostate cancer.Oncogene · 2022Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Increased levels of EZH2, a critical regulator of cellular memory, signal the presence of metastasis and poor outcome in breast cancer patients. High levels of EZH2 are associated with nuclear pleomorphism, lack of estrogen receptor expression, and decreased nuclear levels of BRCA1 tumor suppressor protein in invasive breast carcinomas. The mechanism by which EZH2 overexpression promotes the growth of poorly differentiated invasive carcinomas remains to be defined. Here, we show that EZH2 controls the intracellular localization of BRCA1 protein. Conditional doxycycline-induced upregulation of EZH2 in benign mammary epithelial cells results in nuclear export of BRCA1 protein, aberrant mitoses with extra centrosomes, and genomic instability. EZH2 inhibition in CAL51 breast cancer cells induces BRCA1 nuclear localization and rescues defects in ploidy and mitosis. Mechanistically, EZH2 overexpression is sufficient for activation of the phosphoinositide 3-kinase/Akt (PI3K/Akt) pathway specifically through activation of Akt isoform 1. EZH2-induced BRCA1 nuclear export, aneuploidy, and mitotic defects were prevented by treatment with the PI3K inhibitors LY294002 or wortmannin. Targeted inhibition of Akt-1, Akt-2, and Akt-3 isoforms revealed that the EZH2-induced phenotype requires specific activation of Akt-1. The relevance of our studies to human breast cancer is highlighted by the finding that high EZH2 protein levels are associated with upregulated expression of phospho-Akt-1 (Ser473) and decreased nuclear expression of phospho-BRCA1 (Ser1423) in 39% of invasive breast carcinomas. These results enable us to pinpoint one mechanism by which EZH2 regulates BRCA1 expression and genomic stability mediated by the PI3K/Akt-1 pathway.
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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.