Tumor Biology

, Volume 36, Issue 4, pp 3051–3060 | Cite as

Epstein–Barr virus latent antigens EBNA3C and EBNA1 modulate epithelial to mesenchymal transition of cancer cells associated with tumor metastasis

  • Nivedita Gaur
  • Jaya Gandhi
  • Erle S. Robertson
  • Subhash C. Verma
  • Rajeev Kaul
Research Article

Abstract

Epithelial–mesenchymal transition is an important mechanism in cancer invasiveness and metastasis. We had previously reported that cancer cells expressing Epstein–Barr virus (EBV) latent viral antigens EBV nuclear antigen EBNA3C and/ or EBNA1 showed higher motility and migration potential and had a propensity for increased metastases when tested in nude mice model. We now show that both EBNA3C and EBNA1 can modulate cellular pathways critical for epithelial to mesenchymal transition of cancer cells. Our data confirms that presence of EBNA3C or EBNA1 result in upregulation of transcriptional repressor Slug and Snail, upregulation of intermediate filament of mesenchymal origin vimentin, upregulation of transcription factor TCF8/ZEB1, downregulation as well as disruption of tight junction zona occludens protein ZO-1, downregulation of cell adhesion molecule E-cadherin, and nuclear translocation of β-catenin. We further show that the primary tumors as well as metastasized lesions derived from EBV antigen-expressing cancer cells in nude mice model display EMT markers expression pattern suggesting their greater propensity to mesenchymal transition.

Keywords

EBV Metastasis EMT EBNA3C 

Notes

Acknowledgments

This work was supported by grants from the Department of Biotechnology of Government of India (BT/PR15109/GBD/27/320/2011), MRP grant from UGC (FN-41-1144/2012), R&D grant from the University of Delhi. NG is project fellow funded by UGC, and JG is senior research fellow funded by UGC. ESR is a scholar of the Leukemia and Lymphoma Society of America. SCV is funded by NIH public health grants (CA174459, AI105000). RK is UGC Indo-US Raman research fellow.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Nivedita Gaur
    • 1
  • Jaya Gandhi
    • 1
  • Erle S. Robertson
    • 2
  • Subhash C. Verma
    • 3
  • Rajeev Kaul
    • 1
  1. 1.Department of MicrobiologyUniversity of Delhi South CampusNew DelhiIndia
  2. 2.Department of Microbiology and Tumour Virology Program, Abramson Cancer CentrePerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Microbiology and ImmunologyUniversity of Nevada RenoRenoUSA

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