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EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells
Open accessAbstract
The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer. Here we investigate the functional role of EZH2 in cancer cell invasion and breast cancer progression. EZH2 transcript and protein were consistently elevated in invasive breast carcinoma compared with normal breast epithelia. Tissue microarray analysis, which included 917 samples from 280 patients, demonstrated that EZH2 protein levels were strongly associated with breast cancer aggressiveness. Overexpression of EZH2 in immortalized human mammary epithelial cell lines promotes anchorage-independent growth and cell invasion. EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides compelling evidence for a functional link between dysregulated cellular memory, transcriptional repression, and neoplastic transformation.
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“The increased response rates in EZH2-mutant tumours mirrors preclinical studies and highlights the importance of understanding the mechanisms underlying EZH2 dependence”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [167]
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Cites
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Gupta, R. A., Shah, N., Wang, K., Kim, J., Horlings, H. M., Wong, D. J., Tsai, M.-C., Hung, T., Argani, P., Rinn, J. L., et al. (2010) · Nature · doi:10.1038/nature08975 · Cited by 5,205
Ginestier, C., Hur, M. H., Charafe‐Jauffret, E., Monville, F., Dutcher, J. A., Brown, M., Jacquemier, J. D., Viens, P., Kleer, C. G., Liu, S., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.08.014 · Cited by 4,093
Self-citationThe Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347
Metastasis: from dissemination to organ-specific colonization
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Metadata
- Authors
- Kleer, C. G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S. A., Ghosh, D., Sewalt, R. G. A. B., Otte, A. P., Hayes, D. F., Sabel, M. S., Livant, D., Weiss, S. J., Rubin, M. A., & Chinnaiyan, A. M.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-09-19
- Volume
- 100
- Issue
- 20
- Pages
- 11606-11611
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC208805
- OpenAlex
- W2100365251
- Cited by
- 1,649
- References
- 38
- Citations by year
- 2026: 21 · 2025: 43 · 2024: 53 · 2023: 72 · 2022: 55 · 2021: 67 · 2020: 94 · 2019: 69 · 2018: 83 · 2017: 91 · 2016: 109 · 2015: 109 · 2014: 116 · 2013: 114 · 2012: 108
- FWCI
- 12.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Cancer Institute (P50-CA-69568, R01CA097063, R01 CA97063, P50CA069568)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- EZH2, Polycomb group proteins, breast cancer aggressiveness, breast cancer progression, cell invasion, anchorage-independent growth, oncogenic transformation, mammary epithelial cells, SET domain, histone deacetylase activity, transcriptional repression, cellular memory, prognostic factors
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Breast, Breast Neoplasms, Cell Transformation, Neoplastic, DNA-Binding Proteins, Epithelial Cells, Female, Humans, Immunohistochemistry, Proteins, RNA, Messenger, Transcription Factors, Polymerase Chain Reaction, Polycomb Repressive Complex 2
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