ArticleJournal of virology2012
The Asian-American E6 variant protein of human papillomavirus 16 alone is sufficient to promote immortalization, transformation, and migration of primary human foreskin keratinocytes.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Pre-vaccination prevalence of anogenital and oral human papillomavirus in young HIV-infected men who have sex with men.Papillomavirus research (Amsterdam, Netherlands) · 2019Trial
- Molecular Dynamics and Docking Reveal Enhanced Binding of HPV16 E6 Asian American Variants To non-phosphorylated DLG1.Cell biochemistry and biophysics · 2026Article
- Characterization of patient-derived HPV16 E6 and E7 variant alleles.Journal of virology · 2026Article
- HPV16 Genomes:Current genomics · 2024Article
- The analysis of HPV integration sites based on nanopore sequencing and the profiling changes along the course of photodynamic therapy.BMC cancer · 2023Article
- The ubiquitin specific protease 7 stabilizes HPV16E7 to promote HPV-mediated carcinogenesis.Cellular and molecular life sciences : CMLS · 2023Article
- HPV16 E7 oncoprotein test as a triage strategy for HPV16-positive women in cervical cancer screening: long-term follow-up outcome.Frontiers in oncology · 2023Article
- Genetic diversity of E6, E7 and the long control region in human papillomavirus type 16 variants in Beijing, China.Biochemistry and biophysics reports · 2022Article
- Deep Sequencing of HPV16 E6 Region Reveals Unique Mutation Pattern of HPV16 and Predicts Cervical Cancer.Microbiology spectrum · 2022Article
- The E6 Oncoprotein of HPV16 AA-c Variant Regulates Cell Migration through the MINCR/miR-28-5p/RAP1B Axis.Viruses · 2022Article
- Molecular insights into the interaction of HPV-16 E6 variants against MAGI-1 PDZ1 domain.Scientific reports · 2022Article
- Metabolic Reprogramming in Cancer: Role of HPV 16 Variants.Pathogens (Basel, Switzerland) · 2021Review
- Virus-Host Protein-Protein Interactions between Human Papillomavirus 16 E6 A1 and D2/D3 Sub-Lineages: Variances and Similarities.International journal of molecular sciences · 2020Article
- Human Papillomavirus 58 E7 T20I/G63S Variant Isolated from an East Asian Population Possesses High Oncogenicity.Journal of virology · 2020Article
- An epithelial organoid model with Langerhans cells for assessing virus-host interactions.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Article
- Oncogenic comparison of human papillomavirus type 58 E7 variants.Journal of cellular and molecular medicine · 2019Article
- Human Papillomavirus Type 16International journal of medical sciences · 2019Article
- HPV-6 Molecular Variants Association With the Development of Genital Warts in Men: The HIM Study.The Journal of infectious diseases · 2017Article
- Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology.BMC genomics · 2016Article
- Different Association of Human Papillomavirus 16 Variants with Early and Late Presentation of Cervical Cancer.PloS one · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We examined how well the human papillomavirus (HPV) E6 oncogene can function in the absence of the E7 oncogene during the carcinogenic process in human keratinocytes using a common HPV variant strongly associated with cervical cancer: the Asian-American E6 variant (AAE6). This E6 variant is 20 times more frequently detected in cervical cancer than the prototype European E6 variant, as evidenced by independent epidemiological data. Using cell culture and cell-based functional assays, we assessed how this variant can perform crucial carcinogenesis steps compared to the prototype E6 variant. The ability to immortalize and transform primary human foreskin keratinocytes (PHFKs) to acquire resilient phenotypes and the ability to promote cell migration were evaluated. The immortalization capability was assayed based on population doublings, number of passages, surpassing mortality stages 1 and 2, human telomerase reverse transcriptase (hTERT) expression, and the ability to overcome G(1) arrest via p53 degradation. Transformation and migration efficiency were analyzed using a combination of functional cell-based assays. We observed that either AAE6 or prototype E6 proteins alone were sufficient to immortalize PHFKs, although AAE6 was more potent in doing so. The AAE6 variant protein alone pushed PHFKs through transformation and significantly increased their migration ability over that of the E6 prototype. Our findings are in line with epidemiological data that the AA variant of HPV16 confers an increased risk over the European prototype for cervical cancer, as evidenced by a superior immortalization, transformation, and metastatic potential.
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