ArticleCommunications biology2021
NOTCH and EZH2 collaborate to repress PTEN expression in breast cancer.
Article in Communications biology, 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, 36 citations in OpenAlex.
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Cycloastragenol overcomes trastuzumab resistance in HER2-positive breast cancer by regulating cell cycle and epithelial-mesenchymal transition through EZH2/PTEN/AKT pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The role of Notch signalling and its crosstalk with oestrogen receptor signalling in breast cancer.Cancer metastasis reviews · 2026Review
- Elucidating key targets and mechanisms of diethyl phthalate-induced colorectal cancer through network toxicology and molecular docking.PloS one · 2026Article
- AFF4 promotes tumor progression and cisplatin resistance by modulating the PTEN/PI3K/AKT/mTOR axis to accelerate glycolysis in lung adenocarcinoma.Cell & bioscience · 2025Article
- Review
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Identification of biomarker associated with Trop2 in breast cancer: implication for targeted therapy.Discover oncology · 2024Article
- Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.Discover oncology · 2024Article
- Non-coding RNAs and exosomal non-coding RNAs in lung cancer: insights into their functions.Frontiers in cell and developmental biology · 2024Review
- Notch signaling regulates pulmonary fibrosis.Frontiers in cell and developmental biology · 2024Review
- Article
- Ezh2 promotes mammary tumor initiation through epigenetic regulation of the Wnt and mTORC1 signaling pathways.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Efficacy of CB-103, a First-in-Class Transcriptional Notch Inhibitor, in Preclinical Models of Breast Cancer.Cancers · 2023Article
- The effects of the tumor suppressor geneTranslational cancer research · 2023Article
- The roles of EZH2 in cancer and its inhibitors.Medical oncology (Northwood, London, England) · 2023Review
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- Notch Signaling Promotes Mature T-Cell Lymphomagenesis.Cancer research · 2022Article
- The long and short non-coding RNAs modulating EZH2 signaling in cancer.Journal of hematology & oncology · 2022Review
- Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Downregulation of the PTEN tumor suppressor transcript is frequent in breast cancer and associates with poor prognosis and triple-negative breast cancer (TNBC) when comparing breast cancers to one another. Here we show that in almost all cases, when comparing breast tumors to adjacent normal ducts, PTEN expression is decreased and the PRC2-associated methyltransferase EZH2 is increased. We further find that when comparing breast cancer cases in large cohorts, EZH2 inversely correlates with PTEN expression. Within the highest EZH2 expressing group, NOTCH alterations are frequent, and also associate with decreased PTEN expression. We show that repression of PTEN occurs through the combined action of NOTCH (NOTCH1 or NOTCH2) and EZH2 alterations in a subset of breast cancers. In fact, in cases harboring NOTCH1 mutation or a NOTCH2 fusion gene, NOTCH drives EZH2, HES-1, and HEY-1 expression to repress PTEN transcription at the promoter, which may contribute to poor prognosis in this subgroup. Restoration of PTEN expression can be achieved with an EZH2 inhibitor (UNC1999), a γ-secretase inhibitor (Compound E), or knockdown of EZH2 or NOTCH. These findings elucidate a mechanism of transcriptional repression of PTEN induced by NOTCH1 or NOTCH2 alterations, and identifies actionable signaling pathways responsible for driving a large subset of poor-prognosis breast cancers.
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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.