HPV E6 and E7 oncoproteins cooperatively alter the expression of Disc Large 1 polarity protein in epithelial cells

The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells. The PIR expression was dependent on functional HR-HPV E6 and E7 oncoproteins even though the E7 oncoprotein had higher activity to induce PIR overexpression in comparison with E6. In addition, using an siRNA for PIR silencing in oral cells ectopically expressing HR-HPV E6/E7, there was a significant increase in E-cadherin transcripts and a decrease in Vimentin, Slug, Zeb and Snail transcripts, suggesting that HR-HPV-induced PIR overexpression is involved in epithelial–mesenchymal transition. Furthermore, migration of PIR-silenced cells was significantly decreased. Finally, using inhibitors of some specific pathways, it was found that EGFR/ERK and PI3 K/AKT signalling pathways are important for E7-mediated PIR overexpression. It can be concluded that PIR gene expression is highly dependent on the expression of HR-HPV oncoproteins and is important for EMT regulation.

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Antibody reactivity to HPV E6 and E7 oncoproteins and early diagnosis of invasive cervical cancer

American Journal of Obstetrics and Gynecology ◽

10.1067/mob.2003.97 ◽

2003 ◽

Vol 188 (1) ◽

pp. 3-4 ◽

Cited By ~ 9

Author(s):

Margaret Stanley

Keyword(s):

Cervical Cancer ◽

Early Diagnosis ◽

Invasive Cervical Cancer ◽

Hpv E6 ◽

Antibody Reactivity ◽

E6 And E7 Oncoproteins ◽

E6 And E7

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The Efficacy of Therapeutic DNA Vaccines Expressing the Human Papillomavirus E6 and E7 Oncoproteins for Treatment of Cervical Cancer: Systematic Review

Vaccines ◽

10.3390/vaccines10010053 ◽

2021 ◽

Vol 10 (1) ◽

pp. 53

Author(s):

Ayazhan Akhatova ◽

Chee Kai Chan ◽

Azliyati Azizan ◽

Gulzhanat Aimagambetova

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Public Health Problem ◽

Clinical Implementation ◽

Therapeutic Vaccines ◽

Term Survival ◽

Hpv E6 ◽

E6 And E7 Oncoproteins ◽

E6 And E7 ◽

Lesion Regression

Cervical cancer is recognized as a serious public health problem since it remains one of the most common cancers with a high mortality rate among women despite existing preventative, screening, and treatment approaches. Since Human Papillomavirus (HPV) was recognized as the causative agent, the preventative HPV vaccines have made great progress over the last few years. However, people already infected with the virus require an effective treatment that would ensure long-term survival and a cure. Currently, clinical trials investigating HPV therapeutic vaccines show a promising vaccine-induced T-cell mediated immune response, resulting in cervical lesion regression and viral eradication. Among existing vaccine types (live vector, protein-based, nucleic acid-based, etc.), deoxyribonucleic acid (DNA) therapeutic vaccines are the focus of the study, since they are safe, cost-efficient, thermostable, easily produced in high purity and distributed. The aim of this study is to assess and compare existing DNA therapeutic vaccines in phase I and II trials, expressing HPV E6 and E7 oncoproteins for the prospective treatment of cervical cancer based on clinical efficacy, immunogenicity, viral clearance, and side effects. Five different DNA therapeutic vaccines (GX-188E, VGX-3100, pNGVL4a-CRT/E7(detox), pNGVL4a-Sig/E7(detox)/HSP70, MEDI0457) were well-tolerated and clinically effective. Clinical implementation of DNA therapeutic vaccines into treatment regimen as a sole approach or in combination with conservative treatment holds great potential for effective cancer treatment.

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632. Oncolytic Adenoviruses Targeted to the HPV E6 and E7 Oncoproteins as a Novel Treatment for Head & Neck Squamous Cell Carcinomas

Molecular Therapy ◽

10.1016/s1525-0016(16)34241-1 ◽

2015 ◽

Vol 23 ◽

pp. S251

Author(s):

Christopher J. LaRocca ◽

Amanda Oliveira ◽

Joohee Han ◽

Julia Davydova ◽

Ramon Alemany ◽

...

Keyword(s):

Squamous Cell ◽

Squamous Cell Carcinomas ◽

Oncolytic Adenoviruses ◽

Hpv E6 ◽

Novel Treatment ◽

E6 And E7 Oncoproteins ◽

E6 And E7 ◽

Head Neck

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Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells

PLoS ONE ◽

10.1371/journal.pone.0038178 ◽

2012 ◽

Vol 7 (5) ◽

pp. e38178 ◽

Cited By ~ 18

Author(s):

Juan Pablo Muñoz ◽

Carolina González ◽

Bárbara Parra ◽

Alejandro H. Corvalán ◽

Maria Lina Tornesello ◽

...

Keyword(s):

Human Papillomavirus ◽

Epithelial Cells ◽

Cigarette Smoke ◽

Lung Epithelial Cells ◽

Functional Interaction ◽

Human Papillomavirus Type 16 ◽

Lung Epithelial ◽

E6 And E7 Oncoproteins ◽

E6 And E7

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HPV Oncoproteins and the Ubiquitin Proteasome System: A Signature of Malignancy?

Pathogens ◽

10.3390/pathogens9020133 ◽

2020 ◽

Vol 9 (2) ◽

pp. 133 ◽

Cited By ~ 4

Author(s):

Anamaria Đukić ◽

Lucija Lulić ◽

Miranda Thomas ◽

Josipa Skelin ◽

Nathaniel Edward Bennett Saidu ◽

...

Keyword(s):

Ubiquitin Proteasome System ◽

Cellular Functions ◽

Hpv E6 ◽

System A ◽

Ubiquitin Proteasome ◽

Cellular Pathways ◽

E6 And E7 Oncoproteins ◽

E6 And E7 ◽

Hpv Oncoproteins ◽

Regulation Of Cell Cycle

Human papillomavirus (HPV) E6 and E7 oncoproteins are critical for development and maintenance of the malignant phenotype in HPV-induced cancers. These two viral oncoproteins interfere with a plethora of cellular pathways, including the regulation of cell cycle and the control of apoptosis, which are critical in maintaining normal cellular functions. E6 and E7 bind directly with certain components of the Ubiquitin Proteasome System (UPS), enabling them to manipulate a number of important cellular pathways. These activities are the means by which HPV establishes an environment supporting the normal viral life cycle, however in some instances they can also lead to the development of malignancy. In this review, we have discussed how E6 and E7 oncoproteins from alpha and beta HPV types interact with the components of the UPS, and how this interplay contributes to the development of cancer.

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