ArticleEuropean journal of cancer (Oxford, England : 1990)2016
Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation.
Article in European journal of cancer (Oxford, England : 1990), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Prognostic role of c-Met in head and neck squamous cell cancer tissues: a meta-analysis.Scientific reports · 2018Pooled it
- Targeting metabolic reprogramming in HPV-associated oral squamous cell carcinoma: current advances, challenges, and clinical prospects.Journal of molecular histology · 2026Review
- Advanced Cutaneous Squamous Cell Carcinoma: Biology, Immunotherapy, and Evolving Prognostic Factors.Biomedicines · 2025Review
- Strategies for Anticancer Treatment in p53-Mutated Head and Neck Squamous Cell Carcinoma.Biomedicines · 2025Article
- HPV16 E7 modulates the cell surface expression of MET and CD109 via the AP2 complex.Tumour virus research · 2024Article
- Article
- Radiation modulates expression and related activities of c-Met protein in oral tongue squamous cell carcinoma cell lines.Journal of cancer research and clinical oncology · 2023Article
- DOCK2 contributes to pulmonary fibrosis by promoting lung fibroblast to myofibroblast transition.American journal of physiology. Cell physiology · 2022Article
- DOCK2 Promotes Pleural Fibrosis by Modulating Mesothelial to Mesenchymal Transition.American journal of respiratory cell and molecular biology · 2022Article
- Dedicator of Cytokinesis 2 (DOCK2) Deficiency Attenuates Lung Injury Associated with Chronic High-Fat and High-Fructose Diet-Induced Obesity.The American journal of pathology · 2022Article
- Membrane-Associated RING-CH 8 Functions as a Novel PD-L1 E3 Ligase to Mediate PD-L1 Degradation Induced by EGFR Inhibitors.Molecular cancer research : MCR · 2021Article
- HPV16 E6 enhances the radiosensitivity in HPV-positive human head and neck squamous cell carcinoma by regulating the miR-27a-3p/SMG1 axis.Infectious agents and cancer · 2021Article
- FOXI1 expression in chromophobe renal cell carcinoma and renal oncocytoma: a study of The Cancer Genome Atlas transcriptome-based outlier mining and immunohistochemistry.Virchows Archiv : an international journal of pathology · 2021Article
- Article
- MiR-23b-3p reduces the proliferation, migration and invasion of cervical cancer cell lines via the reduction of c-Met expression.Scientific reports · 2020Article
- Clinicopathological impacts of high c-Met expression in head and neck squamous cell carcinoma: a meta-analysis and review.Oncotarget · 2017Article
- Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment.Cancers · 2017Review
- The Interaction Between Human Papillomaviruses and the Stromal Microenvironment.Progress in molecular biology and translational science · 2016Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeHuman papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) carries a distinct clinical behaviour. c-Met oncogene is an important driver for tumour progression and its relationship with HPV in OPSCC was explored in the present study. EXPERIMENTAL
designKnockdown of HPV oncogene E6 or p53 alone and in combination was performed to examine their effects on c-Met expression by Western blot and quantitative real-time polymerase chain reaction. The effects of c-Met inhibition on cell proliferation, migration, and colony formation were examined in HPV-positive head and neck squamous cell carcinoma (HNSCC) cells. Retrospectively collected OPSCC patient specimens (N = 78) were stained for c-Met by immunohistochemistry and the staining levels were correlated with HPV status and patient outcomes.
resultsE6 knockdown decreased c-Met protein and mRNA expression in HPV-positive HNSCC cells, which was partially abolished by the elimination of p53. Reducing c-Met decreased cell proliferation, migration, and colony formation in HPV-positive HNSCC cells. In OPSCC patient samples, high c-Met expression was associated with HPV-positive status (OR = 4.11, 95%CI: 1.16-14.55, P = 0.028) and tumour stage (OR = 0.27, 95%CI: 0.08-0.93, P = 0.039) by multivariable analysis. In T3/T4 stage patients, high c-Met expression was associated with HPV positivity and low p53 levels, supporting an axis of E6-p53-c-Met regulation. Furthermore, high c-Met expression was marginally associated with poor disease-free survival in HPV-positive patients.
conclusionsOur results suggest that c-Met may serve as a novel target for treating HPV-associated OPSCC. The data also demonstrate that HPV E6 upregulates c-Met expression partially through p53 downregulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.