ArticleEBioMedicine2022
Polyploid giant cancer cells, EZH2 and Myc upregulation in mammary epithelial cells infected with high-risk human cytomegalovirus.
Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 46 citations in OpenAlex.
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- Clinical Implications of Polyploid Giant Cancer Cells in Solid Tumors: Biology, Diagnosis, and Therapeutic Considerations.Cancers · 2026Review
- CMV seropositivity associates with poor clinical outcome in triple negative breast cancer.iScience · 2026Article
- Review
- Does human cytomegalovirus provide a novel therapeutic target for patients with glioblastoma?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- The Impact of Polyploid Giant Cancer Cells: The Root of Stress Resilience.Cancer science · 2025Review
- Re-evaluating CD57 as a marker of T cell senescence: implications for immune ageing and differentiation.Immunity & ageing : I & A · 2025Article
- Review
- Review
- Human Cytomegalovirus Infection and Breast Cancer: A Literature Review of Clinical and Experimental Data.Biology · 2025Review
- Paxillin promotes the invasion and migration of polyploid giant cancer cells with daughter cells after arsenic trioxide treatment by regulating the expression of cathepsin B/D.Journal of Cancer · 2025Article
- Polyploid giant cancer cells and tumor budding: translation from basic research to clinical application.Frontiers in oncology · 2025Review
- Identification of B cell antigens in solid cancer: initial insights and functional implications.Frontiers in immunology · 2025Review
- HPV and HCMV in Cervical Cancer: A Review of Their Co-Occurrence in Premalignant and Malignant Lesions.Viruses · 2024Review
- Article
- Review
- Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies.Biomarker research · 2024Review
- Generation of glioblastoma in mice engrafted with human cytomegalovirus-infected astrocytes.Cancer gene therapy · 2024Article
- Adaptive natural killer cell expression in response to cytomegalovirus infection in blood and solid cancer.Heliyon · 2024Review
- The Role of Oncogenic Viruses in the Pathogenesis of Sporadic Breast Cancer: A Comprehensive Review of the Current Literature.Pathogens (Basel, Switzerland) · 2024Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman cytomegalovirus (HCMV) infection has been actively implicated in complex neoplastic processes. Beyond oncomodulation, the molecular mechanisms that might underlie HCMV-induced oncogenesis are being extensively studied. Polycomb repressive complex 2 (PRC2) proteins, in particular enhancer of zeste homolog 2 (EZH2) are associated with cancer progression. Nevertheless, little is known about EZH2 activation in the context of HCMV infection and breast oncogenesis.
methodsHerein, we identified EZH2 as a downstream target for HCMV-induced Myc upregulation upon acute and chronic infection with high-risk strains using a human mammary epithelial model.
findingsWe detected polyploidy and CMV-transformed HMECs (CTH) cells harboring HCMV and dynamically undergoing the giant cells cycle. Acquisition of embryonic stemness markers positively correlated with EZH2 and Myc expression. EZH2 inhibitors curtail sustained CTH cells' malignant phenotype. Besides harboring polyploid giant cancer cells (PGCCs), tumorigenic breast biopsies were characterized by an enhanced EZH2 and Myc expression, with a strong positive correlation between EZH2 and Myc expression, and between PGCC count and EZH2/Myc expression in the presence of HCMV. Further, we isolated two HCMV strains from EZH2
interpretationOur data establish a potential link between HCMV-induced Myc activation, the subsequent EZH2 upregulation, and polyploidy induction. These data support the proposed tumorigenesis properties of EZH2/Myc, and allow the isolation of two oncogenic HCMV strains from EZH2
fundingThis work was supported by grants from the University of Franche-Comté (UFC) (CR3300), the Région Franche-Comté (2021-Y-08292 and 2021-Y-08290) and the Ligue contre le Cancer (CR3304) to Georges Herbein. Zeina Nehme is a recipient of a doctoral scholarship from the municipality of Habbouch. Sandy Haidar Ahmad is recipient of a doctoral scholarship from Lebanese municipality. Ranim El Baba is a recipient of a doctoral scholarship from Hariri foundation for sustainable human development.
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