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Polyploid giant cancer cells, stemness and epithelial-mesenchymal plasticity elicited by human cytomegalovirus

Oncogene volume 40, pages 3030–3046 (2021)Cite this article

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Abstract

A growing body of evidence is recognizing human cytomegalovirus (HCMV) as a potential oncogenic virus. We hereby provide the first experimental in vitro evidence for HCMV as a reprogramming vector, through the induction of dedifferentiation of mature human mammary epithelial cells (HMECs), generation of a polyploid giant cancer cell (PGCC) phenotype characterized by sustained growth of blastomere-like cells, in concordance with the acquisition of embryonic stem cells characteristics and epithelial-mesenchymal plasticity. HCMV presence parallels the succession of the observed cellular and molecular events potentially ensuing the transformation process. Correlation between PGCCs detection and HCMV presence in breast cancer tissue further validates our hypothesis in vivo. Our study indicates that some clinical HCMV strains conserve the potential to transform HMECs and fit with a “blastomere-like” model of oncogenesis, which may be relevant in the pathophysiology of breast cancer and other adenocarcinoma, especially of poor prognosis.

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Fig. 1: Activation of oncogenic pathways, differential apoptosis rates and upregulation of telomerase activity in HMECs infected by HCMV clinical strains.
Fig. 2: Colony formation in soft agar, chronic infection of HMECs with HCMV clinical isolates and the appearance of distinct cellular features of the giant cell cycle including polyploid giant cancer cells (PGCCs).
Fig. 3: Detection of polyploidy, anchorage-independent growth and proliferative capacity of CTH cells.
Fig. 4: Phenotypic characterization of CTH cells.
Fig. 5: Mammospheres formation and detection of embryonic stem cells markers in CTH cells.
Fig. 6: Detection of replicative HCMV in CTH culture.
Fig. 7: Transcriptomic analysis of CTH cells, PGCCs detection and correlation with HCMV in human breast tumor biopsies.
Fig. 8: Potential model depicting the course of events leading to the initiation of the giant cell cycle, dedifferentiation, stemness and epithelial-to-mesenchymal/mesenchymal-to-epithelial transitions following HCMV infection.

Data availability

The data supporting the findings of this study are available within the article and its Supplementary Information files and from the corresponding authors on request.

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. Dimri G, Band H, Band V. Mammary epithelial cell transformation: insights from cell culture and mouse models. Breast Cancer Res. 2005;7:171–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Polyak K. Heterogeneity in breast cancer. J Clin Investig. 2011;121:3786–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dai X, Li T, Bai Z, Yang Y, Liu X, Zhan J, et al. Breast cancer intrinsic subtype classification, clinical use and future trends. Am J Cancer Res. 2015;5:2929–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hüsing A, Canzian F, Beckmann L, Garcia-Closas M, Diver WR, Thun MJ, et al. Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status. J Med Genet. 2012;49:601–8.

    Article  PubMed  Google Scholar 

  6. Morales-Sánchez A, Fuentes-Pananá EM. Human viruses and cancer. Viruses. 2014;6:4047–79.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Coaquette A, Bourgeois A, Dirand C, Varin A, Chen W, Herbein G. Mixed cytomegalovirus glycoprotein B genotypes in immunocompromised patients. Clin Infect Dis. 2004;39:155–61.

    Article  PubMed  Google Scholar 

  8. Sinzger C, Digel M, Jahn G Cytomegalovirus Cell Tropism. In: Shenk TE, Stinski MF (eds). Human Cytomegalovirus. Springer-Verlag: Berlin-Heidelberg, 2008, pp 63–83.

  9. Michaelis M, Doerr HW, Cinatl J. The story of human cytomegalovirus and cancer: increasing evidence and open questions. Neoplasia. 2009;11:1–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, et al. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002;62:3347–50.

    CAS  PubMed  Google Scholar 

  11. Taher C, de Boniface J, Mohammad A-A, Religa P, Hartman J, Yaiw K-C, et al. High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes. PLoS ONE. 2013;8:e56795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kumar A, Tripathy MK, Pasquereau S, Al Moussawi F, Abbas W, Coquard L, et al. The human cytomegalovirus strain DB activates oncogenic pathways in mammary epithelial cells. EBioMedicine. 2018;30:167–83.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Geder KM, Lausch R, O’Neill F, Rapp F. Oncogenic transformation of human embryo lung cells by human cytomegalovirus. Science. 1976;192:1134–7.

    Article  CAS  PubMed  Google Scholar 

  14. Niu N, Mercado-Uribe I, Liu J. Dedifferentiation into blastomere-like cancer stem cells via formation of polyploid giant cancer cells. Oncogene. 2017;36:4887–4900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang S, Mercado-Uribe I, Xing Z, Sun B, Kuang J, Liu J. Generation of cancer stem-like cells through the formation of polyploid giant cancer cells. Oncogene. 2014;33:116–28.

    Article  CAS  PubMed  Google Scholar 

  16. Niu N, Zhang J, Zhang N, Mercado-Uribe I, Tao F, Han Z, et al. Linking genomic reorganization to tumor initiation via the giant cell cycle. Oncogenesis. 2016;5:e281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Al Moussawi F, Kumar A, Pasquereau S, Tripathy MK, Karam W, Diab-Assaf M et al. The transcriptome of human mammary epithelial cells infected with the HCMV-DB strain displays oncogenic traits. Sci Rep. 2018;8. https://doi.org/10.1038/s41598-018-30109-1.

  18. Collins-McMillen D, Rak M, Buehler JC, Igarashi-Hayes S, Kamil JP, Moorman NJ, et al. Alternative promoters drive human cytomegalovirus reactivation from latency. Proc Natl Acad Sci USA. 2019;116:17492–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lee EYHP, Muller WJ. Oncogenes and Tumor Suppressor Genes. Cold Spring Harb Perspect Biol. 2010;2. https://doi.org/10.1101/cshperspect.a003236.

  20. Prichard MN, Sztul E, Daily SL, Perry AL, Frederick SL, Gill RB, et al. Human cytomegalovirus UL97 kinase activity is required for the hyperphosphorylation of retinoblastoma protein and inhibits the formation of nuclear aggresomes. J Virol. 2008;82:5054–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tsai HL, Kou GH, Chen SC, Wu CW, Lin YS. Human cytomegalovirus immediate-early protein IE2 tethers a transcriptional repression domain to p53. J Biol Chem. 1996;271:3534–40.

    Article  CAS  PubMed  Google Scholar 

  22. Knudsen ES, McClendon AK, Franco J, Ertel A, Fortina P, Witkiewicz AK. RB loss contributes to aggressive tumor phenotypes in MYC-driven triple negative breast cancer. Cell Cycle. 2015;14:109–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhao JJ, Gjoerup OV, Subramanian RR, Cheng Y, Chen W, Roberts TM, et al. Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase. Cancer Cell. 2003;3:483–95.

    Article  CAS  PubMed  Google Scholar 

  24. Cojohari O, Peppenelli MA, Chan GC. Human cytomegalovirus induces an atypical activation of Akt to stimulate the survival of short-lived monocytes. J Virol. 2016;90:6443–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Luo J, Yan R, He X, He J. Constitutive activation of STAT3 and cyclin D1 overexpression contribute to proliferation, migration and invasion in gastric cancer cells. Am J Transl Res. 2017;9:5671–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Newbold RF. The significance of telomerase activation and cellular immortalization in human cancer. Mutagenesis. 2002;17:539–50.

    Article  CAS  PubMed  Google Scholar 

  27. Strååt K, Liu C, Rahbar A, Zhu Q, Liu L, Wolmer-Solberg N, et al. Activation of telomerase by human cytomegalovirus. J Natl Cancer Inst. 2009;101:488–97.

    Article  PubMed  Google Scholar 

  28. Romaniuk A, Paszel-Jaworska A, Totoń E, Lisiak N, Hołysz H, Królak A, et al. The non-canonical functions of telomerase: to turn off or not to turn off. Mol Biol Rep. 2019;46:1401–11.

    Article  CAS  PubMed  Google Scholar 

  29. White E. Mechanisms of apoptosis regulation by viral oncogenes in infection and tumorigenesis. Cell Death Differ. 2006;13:1371–7.

    Article  CAS  PubMed  Google Scholar 

  30. Xiong S, Feng Y, Cheng L. Cellular reprogramming as a therapeutic target in cancer. Trends Cell Biol. 2019;29:623–34.

    Article  CAS  PubMed  Google Scholar 

  31. Zheng L, Dai H, Zhou M, Li X, Liu C, Guo Z, et al. Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression. Nat Commun. 2012;3:815.

    Article  PubMed  Google Scholar 

  32. McFarlane S, Nicholl MJ, Sutherland JS, Preston CM. Interaction of the human cytomegalovirus particle with the host cell induces hypoxia-inducible factor 1 alpha. Virology. 2011;414:83–90.

    Article  CAS  PubMed  Google Scholar 

  33. Weljie AM, Jirik FR. Hypoxia-induced metabolic shifts in cancer cells: Moving beyond the Warburg effect. Int J Biochem Cell Biol. 2011;43:981–9.

    Article  CAS  PubMed  Google Scholar 

  34. Yu Y, Clippinger AJ, Alwine JC. Viral affects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol. 2011;19:360–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yin X, Grove L, Datta NS, Long MW, Prochownik EV. C- myc overexpression and p53 loss cooperate to promote genomic instability. Oncogene. 1999;18:1177–84.

    Article  CAS  PubMed  Google Scholar 

  36. Hein SM, Haricharan S, Johnston AN, Toneff MJ, Reddy JP, Dong J, et al. Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress. Oncogene. 2016;35:1461–7.

    Article  CAS  PubMed  Google Scholar 

  37. Rodilla V, Fre S Cellular plasticity of mammary epithelial cells underlies heterogeneity of breast cancer. Biomedicines. 2018;6. https://doi.org/10.3390/biomedicines6040103.

  38. Tata PR, Mou H, Pardo-Saganta A, Zhao R, Prabhu M, Law BM, et al. Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature. 2013;503:218–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yu W, Ma Y, Ochoa AC, Shankar S, Srivastava RK. Cellular transformation of human mammary epithelial cells by SATB2. Stem Cell Res. 2017;19:139–47.

    Article  CAS  PubMed  Google Scholar 

  40. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  41. Liu J. The dualistic origin of human tumors. Semin Cancer Biol. 2018;53:1–16.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Liu J. The ‘life code’: a theory that unifies the human life cycle and the origin of human tumors. Semin Cancer Biol. 2020;60:380–97.

    Article  CAS  PubMed  Google Scholar 

  43. Odeberg J, Wolmer N, Falci S, Westgren M, Seiger Å, Söderberg-Nauclér C. Human cytomegalovirus inhibits neuronal differentiation and induces apoptosis in human neural precursor cells. J Virol. 2006;80:8929–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Luo MH, Hannemann H, Kulkarni AS, Schwartz PH, O’Dowd JM, Fortunato EA. Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells. J Virol. 2010;84:3528–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fei F, Zhang D, Yang Z, Wang S, Wang X, Wu Z et al. The number of polyploid giant cancer cells and epithelial-mesenchymal transition-related proteins are associated with invasion and metastasis in human breast cancer. J Exp Clin Cancer Res. 2015;34. https://doi.org/10.1186/s13046-015-0277-8.

  46. Liu S, Cong Y, Wang D, Sun Y, Deng L, Liu Y, et al. Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts. Stem Cell Rep. 2014;2:78–91.

    Article  CAS  Google Scholar 

  47. Wang M-H, Sun R, Zhou X-M, Zhang M-Y, Lu J-B, Yang Y, et al. Epithelial cell adhesion molecule overexpression regulates epithelial-mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN/AKT/mTOR pathway. Cell Death Dis. 2018;9:2.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Yamashita N, Tokunaga E, Iimori M, Inoue Y, Tanaka K, Kitao H, et al. Epithelial paradox: clinical significance of coexpression of E-cadherin and vimentin with regard to invasion and metastasis of breast cancer. Clin Breast Cancer. 2018;18:e1003–e1009.

    Article  CAS  PubMed  Google Scholar 

  49. Pastushenko I, Brisebarre A, Sifrim A, Fioramonti M, Revenco T, Boumahdi S, et al. Identification of the tumour transition states occurring during EMT. Nature. 2018;556:463–8.

    Article  CAS  PubMed  Google Scholar 

  50. Høffding MK, Hyttel P. Ultrastructural visualization of the mesenchymal-to-epithelial transition during reprogramming of human fibroblasts to induced pluripotent stem cells. Stem Cell Res. 2015;14:39–53.

    Article  PubMed  Google Scholar 

  51. Oberstein A, Shenk T. Cellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype. PNAS. 2017;114:E8244–E8253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lopez-Sánchez LM, Jimenez C, Valverde A, Hernandez V, Peñarando J, Martinez A et al. CoCl2, a Mimic of Hypoxia, Induces Formation of Polyploid Giant Cells with Stem Characteristics in Colon Cancer. PLoS ONE. 2014;9. https://doi.org/10.1371/journal.pone.0099143.

  53. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lawson DA, Bhakta NR, Kessenbrock K, Prummel KD, Yu Y, Takai K, et al. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature. 2015;526:131–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008;40:499–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tanabe K, Nakamura M, Narita M, Takahashi K, Yamanaka S. Maturation, not initiation, is the major roadblock during reprogramming toward pluripotency from human fibroblasts. Proc Natl Acad Sci USA. 2013;110:12172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ling G-Q, Chen D-B, Wang B-Q, Zhang L-S. Expression of the pluripotency markers Oct3/4, Nanog and Sox2 in human breast cancer cell lines. Oncol Lett. 2012;4:1264–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Huang Y-H, Luo M-H, Ni Y-B, Tsang JYS, Chan S-K, Lui PCW, et al. Increased SOX2 expression in less differentiated breast carcinomas and their lymph node metastases. Histopathology. 2014;64:494–503.

    Article  PubMed  Google Scholar 

  59. Wang D, Lu P, Zhang H, Luo M, Zhang X, Wei X, et al. Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients. Oncotarget. 2014;5:10803–15.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Lu X, Mazur SJ, Lin T, Appella E, Xu Y. The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis. Oncogene. 2014;33:2655–64.

    Article  CAS  PubMed  Google Scholar 

  61. Aloia A, Petrova E, Tomiuk S, Bissels U, Déas O, Saini M. et al. The sialyl-glycolipid stage-specific embryonic antigen 4 marks a subpopulation of chemotherapy-resistant breast cancer cells with mesenchymal features. Breast Cancer Res. 2015;17. https://doi.org/10.1186/s13058-015-0652-6.

  62. Chuang P-K, Hsiao M, Hsu T-L, Chang C-F, Wu C-Y, Chen B-R, et al. Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer. PNAS. 2019;116:3518–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Yu K-R, Yang S-R, Jung J-W, Kim H, Ko K, Han DW, et al. CD49f enhances multipotency and maintains stemness through the direct regulation of OCT4 and SOX2. Stem Cells. 2012;30:876–87.

    Article  CAS  PubMed  Google Scholar 

  64. Fornara O, Bartek J, Rahbar A, Odeberg J, Khan Z, Peredo I, et al. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact. Cell Death Differ. 2016;23:261–9.

    Article  CAS  PubMed  Google Scholar 

  65. Soroceanu L, Matlaf L, Khan S, Akhavan A, Singer E, Bezrookove V, et al. Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma. Cancer Res. 2015;75:3065–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Jha HC, Banerjee S, Robertson ES The Role of Gammaherpesviruses in Cancer Pathogenesis. Pathogens. 2016;5. https://doi.org/10.3390/pathogens5010018.

  67. Belzile J-P, Stark TJ, Yeo GW, Spector DH. Human cytomegalovirus infection of human embryonic stem cell-derived primitive neural stem cells is restricted at several steps but leads to the persistence of viral DNA. J Virol. 2014;88:4021–39.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Heieren MH, Kim YK, Balfour HH. Human cytomegalovirus infection of kidney glomerular visceral epithelial and tubular epithelial cells in culture. Transplantation. 1988;46:426–32.

    Article  CAS  PubMed  Google Scholar 

  69. Furukawa T. A variant of human cytomegalovirus derived from a persistently infected culture. Virology. 1984;137:191–4.

    Article  CAS  PubMed  Google Scholar 

  70. Coronel R, Takayama S, Juwono T, Hertel L. Dynamics of human cytomegalovirus infection in CD34+ hematopoietic cells and derived Langerhans-type dendritic cells. J Virol. 2015;89:5615–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Manners O, Murphy JC, Coleman A, Hughes DJ, Whitehouse A. Contribution of the KSHV and EBV lytic cycles to tumourigenesis. Curr Opin Virol. 2018;32:60–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Münz C. Latency and lytic replication in Epstein–Barr virus-associated oncogenesis. Nat Rev Microbiol. 2019;17:691–700.

    Article  PubMed  Google Scholar 

  73. Ganem D. KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. J Clin Investig. 2010;120:939–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Herbein G, Nehme Z. Polyploid giant cancer cells, a hallmark of oncoviruses and a new therapeutic challenge. Front Oncol. 2020;10:567116.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Khan KA, Coaquette A, Davrinche C, Herbein G. Bcl-3-regulated transcription from major immediate-early promoter of human cytomegalovirus in monocyte-derived macrophages. J Immunol. 2009;182:7784–94.

    Article  CAS  PubMed  Google Scholar 

  76. Lepiller Q, Abbas W, Kumar A, Tripathy MK, Herbein G. HCMV activates the IL-6-JAK-STAT3 axis in HepG2 cells and primary human hepatocytes. PLOS ONE. 2013;8:e59591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by grants from the University of Franche-Comté, and the Région Franche-Comté. Z.N. is a recipient of a doctoral scholarship from the municipality of Habbouch. The funders had no role in the data collection, analysis, patient recruitment, or decision to publish. We thank DImaCell Imaging Ressource Center, University of Bourgogne Franche-Comté, Faculty of Health Sciences, 25000 Besançon, France for technical support.

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Authors and Affiliations

  1. Department Pathogens & Inflammation-EPILAB EA4266, University of Bourgogne France-Comté, Besançon, France

    Zeina Nehme, Sébastien Pasquereau, Sandy Haidar Ahmad & Georges Herbein

  2. Lebanese University, Beyrouth, Lebanon

    Zeina Nehme, Sandy Haidar Ahmad & Mona Diab Assaf

  3. Department of Virology, CHRU Besançon, Besançon, France

    Alain Coaquette & Georges Herbein

  4. Department of Pathology, CHRU Besançon, Besançon, France

    Chloé Molimard, Franck Monnien & Marie-Paule Algros

  5. INSERM, EFS BFC, UMR1098, RIGHT, University of Bourgogne Franche-Comté, Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France

    Olivier Adotevi & Jean-Paul Feugeas

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Contributions

ZN, SP, SHA, AC, CM, FM performed experiments. GH, M-PA., OA, MDA, JPF participated to the data analysis. GH conceived and designed the project. ZN, SP, JPF, GH wrote the manuscript.

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Correspondence to Georges Herbein.

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Nehme, Z., Pasquereau, S., Haidar Ahmad, S. et al. Polyploid giant cancer cells, stemness and epithelial-mesenchymal plasticity elicited by human cytomegalovirus. Oncogene 40, 3030–3046 (2021). https://doi.org/10.1038/s41388-021-01715-7

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