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Cdc6 expression is induced by HPV16 E6 and E7 oncogenes and represses E-cadherin expression

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An Addendum to this article was published on 06 February 2020

Abstract

Cervical cancer is one of the most common cancers in women worldwide, and its development is related to two viral oncoproteins E6 and E7 from high-risk human papillomaviruses. Aberrant expression of E-cadherin is associated with epithelial-to-mesenchymal transition (EMT), and it is frequently seen in cervical cancer. However, the underlying mechanisms involved in E-cadherin suppression in cervical cancer are not clear. We studied the effects of human papillomavirus 16 (HPV16) E6 and E7 on E-cadherin and Cdc6 (cell division cycle 6) expression in the HCT-116 cell line. We also assessed the relationship between Cdc6 and E-cadherin expression in cells expressing HPV16 E6 and E7 proteins. The results showed that HPV16 E6 and E7 proteins reduce E-cadherin expression, and HPV16 E6-expressing cells undergo a more profound suppression of E-cadherin compared with cells expressing HPV16 E7. Our results also revealed that HPV16 E6 and E7 oncoproteins induce Cdc6 expression, whereas suppression of Cdc6 protein by short hairpin RNA restores E-cadherin expression. Induction of Cdc6 expression in HCT-116 cells was greater with E6 than with E7, a finding that was consistent with the corresponding changes in E-cadherin expression. These observations suggest that Cdc6 overexpression is an important factor for E-cadherin reduction in cells expressing HPV16 E6 and E7 proteins and may have an important role in the metastasis of HPV-associated cancers.

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Acknowledgements

We thank the entire staff of the Department of Virology, School of Public Health, Tehran University of Medical Sciences. This research was supported by Tehran University of Medical Sciences under research no. 93-03-27-25127.

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Correspondence to T Mokhtari-Azad.

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Faghihloo, E., Sadeghizadeh, M., Shahmahmoodi, S. et al. Cdc6 expression is induced by HPV16 E6 and E7 oncogenes and represses E-cadherin expression. Cancer Gene Ther (2016). https://doi.org/10.1038/cgt.2016.51

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