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Original Research ARTICLE

Front. Oncol. | doi: 10.3389/fonc.2021.630408

Oncoproteins of high-risk HPV and EBV cooperate to enhance cell motility and invasion of human breast cancer cells via Erk1/Erk2 and -catenin signaling pathways Provisionally accepted The final, formatted version of the article will be published soon. Notify me

 Ishita Gupta1, Ayesha Jabeen1,  Semir Vranic1,  Ala-Eddin Al Moustafa2* and Hamda Al-Thawad1*
  • 1Qatar University, Qatar
  • 2College of Medicine of Qatar University, Qatar University, Qatar

Breast cancer is a leading cause of death in women around the world. Most of breast cancer-related deaths are a result of complications from the metastatic spread. Several recent studies reported that high-risk human papillomaviruses (HPVs) and Epstein-Barr virus (EBV) are co-present in different types of human carcinomas including breast; however, the cooperative effects between high-risk HPVs and EBV oncoproteins in human breast cancer have not been investigated yet. Thus, we herein explored the cooperation outcome between E6/E7 and LMP1 oncoproteins of high-risk HPV type 16 and EBV, respectively, in two human breast cancer cell lines, MCF7 and MDA-MB-231. Our data revealed that E6/E7 and LMP1 oncoproteins cooperation stimulate cell proliferation and deregulate cell cycle progression of human breast cancer cells; in parallel, we noted that E6/E7/LMP1 incite colony formation of both cell lines. More significantly, our results point out that co-expression of E6/E7 and LMP1 oncoproteins enhances cell motility and invasion of MCF7 and MDA-MB-231 cell lines; this is accompanied by deregulation of epithelial-mesenchymal transition biomarkers including E-cadherin, -catenin, fascin and vimentin. The molecular pathway analysis of HPV and EBV oncoproteins cooperation shows that it can enhance the phosphorylation of Erk1/Erk2 in addition to -catenin, which could be behind the effect of this cooperation in our cell models. The study clearly suggests that high-risk HPV and EBV co-infection can play an important role in breast cancer progression via Erk1/Erk2 and β-catenin signaling pathways.

Keywords: breast cancer, Gene deregulation, HPV, ebv, In-vitro, oncoproteins, HPV – human papillomavirus

Received: 17 Nov 2020; Accepted: 08 Feb 2021.

Copyright: © 2021 Gupta, Jabeen, Vranic, Al Moustafa and Al-Thawad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Ala-Eddin Al Moustafa, Qatar University, College of Medicine of Qatar University, Doha, Qatar, ala-eddin.almoustafa@mcgill.ca
Dr. Hamda Al-Thawad, Qatar University, Doha, Qatar, halthawadi@qu.edu.qa