Human cytomegalovirus infection enhances cell proliferation, migration and upregulation of EMT markers in colorectal cancer-derived stem cell-like cells

Wan Huai Teo, Hsin Pai Chen, Jason C. Huang*, Yu Jiun Chan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Increasing evidence suggests a link between persistent human cytomegalovirus (HCMV) infection and cancer. Although the role of HCMV in cancer is still elusive, recent studies revealed the presence of HCMV nucleic acids and proteins in different cancer types such as glioblastoma, colorectal, breast, and prostate cancers, and neuroblastoma. Although HCMV may not be directly associated with the neoplastic transformation, the presence of HCMV DNA in the tumorous tissue has been associated with altered clinical outcomes in cancer patients. However, the mechanisms involved in the association between colorectal cancer (CRC) and HCMV are unclear. In this study, we investigated the influence of HCMV infection on CRC or their derived cells. Proliferation and migration assays revealed a high infection efficiency in CRC-derived HT29 and SW480 stem-like cells. After 24, 48 and 72 h of HCMV infection, both HT29 and SW480 parental and stem.like cells showed a significant increse in cell proliferation and viability (p<0.0001). Moreover, HCMV infection promoted cell migration. These results demonstrate a significant phenotypic alteration in the CRC cell line upon HCMV infection. Using epithelial to mesenchymal transition (EMT) assays, we demonstrated that the EMT markers and driver genes were upregulated during the virus infection. The WNT signaling pathway, which is associated with the proliferation and migration of CRC cells, was upregulated (6-fold) in HCMV-infected cells as compared to the non-infected cells at day 7 from infection.

Original languageEnglish
Pages (from-to)1415-1426
Number of pages12
JournalInternational journal of oncology
Volume51
Issue number5
DOIs
StatePublished - Nov 2017

Keywords

  • CD44
  • Colorectal cancer
  • Epithelial to mesenchymal transition
  • Human cytomegalovirus
  • Migration
  • Proliferation
  • WNT pathway

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