Oncoproteins of High-Risk HPV and EBV Cooperate to Enhance Cell Motility and Invasion of Human Breast Cancer Cells Erk1/Erk2 and β-Catenin Signaling Pathways.
Author | Gupta, Ishita |
Author | Jabeen, Ayesha |
Author | Vranic, Semir |
Author | Al Moustafa, Ala-Eddin |
Author | Al-Thawadi, Hamda |
Available date | 2021-04-27T07:12:29Z |
Publication Date | 2021-03-12 |
Publication Name | Frontiers in Oncology |
Identifier | http://dx.doi.org/10.3389/fonc.2021.630408 |
Citation | Gupta I, Jabeen A, Vranic S, Al Moustafa AE and Al-Thawadi H (2021) Oncoproteins of High-Risk HPV and EBV Cooperate to Enhance Cell Motility and Invasion of Human Breast Cancer Cells via Erk1/Erk2 and β-Catenin Signaling Pathways. Front. Oncol. 11:630408. doi: 10.3389/fonc.2021.630408 |
Abstract | Breast cancer is a leading cause of death in women around the world. Most 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-presented 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 latent membrane protein 1 (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 the cooperation of E6/E7 and LMP1 oncoproteins stimulates cell proliferation and deregulates cell cycle progression of human breast cancer and normal mammary cells; in parallel, we noted that E6/E7/LMP1 incite colony formation of both breast cancer cell lines but not normal cells. More significantly, our results point out that the 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, β-catenin, fascin, and vimentin. The molecular pathway analysis of HPV and EBV oncoproteins cooperation shows that it can enhance the phosphorylation of extracellular signal-regulated kinases (Erk1/Erk2) in addition to β-catenin, which could be behind the effect of this cooperation in our cell models. The study clearly suggests that high-risk HPV and EBV coinfection can play an important role in breast cancer progression Erk1/Erk2 and β-catenin signaling pathways. |
Sponsor | grants from Qatar University: QUCG-CMED-2018/2019-3, QUHI-CMED-19/20-1, and QUCG-CMED-20/21-2. |
Language | en |
Publisher | Frontiers Media |
Subject | EBV HPV breast cancer gene deregulation in-vitro oncoproteins |
Type | Article |
Volume Number | 11 |
ESSN | 2234-943X |
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