ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2015
The protective effect of p16(INK4a) in oral cavity carcinomas: p16(Ink4A) dampens tumor invasion-integrated analysis of expression and kinomics pathways.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Pterygomandibular raphe invasion as a novel grading and prognostic factor for squamous cell carcinoma of buccal mucosa: a retrospective study with propensity score matching.International journal of clinical oncology · 2025Article
- Comparison of mutation landscapes of pretreatment versus recurrent squamous cell carcinoma of the oral cavity: The possible mechanism of resistance to standard treatment.Cancer reports (Hoboken, N.J.) · 2024Article
- Prevalence of high-risk human papillomavirus in oral squamous cell carcinoma with or without chewing habits.PloS one · 2024Article
- Association between human papillomavirus and oral cancer: a literature review.International journal of clinical oncology · 2023Review
- The multifaceted role of STAT3 pathway and its implication as a potential therapeutic target in oral cancer.Archives of pharmacal research · 2022Review
- KRSA: An R package and R Shiny web application for an end-to-end upstream kinase analysis of kinome array data.PloS one · 2021Article
- The expression and prognostic impact of proinflammatory cytokines and their associations with carcinogens in oropharyngeal squamous cell carcinoma.Cancer immunology, immunotherapy : CII · 2020Article
- Combining PARP and DNA-PK Inhibitors With Irradiation Inhibits HPV-Negative Head and Neck Cancer Squamous Carcinoma Growth.Frontiers in genetics · 2020Article
- Prognostic impact of extratumoral perineural invasion in patients with oral cavity squamous cell carcinoma.Cancer medicine · 2019Article
- Expression and Significance of Cytokeratin 7, a Squamocolumnar Junction Marker, in Head and Neck Squamous Cell Carcinoma.Head and neck pathology · 2018Article
- Cancer stage and pack-years, but not p16 or HPV, are relevant for survival in hypopharyngeal and laryngeal squamous cell carcinomas.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2018Article
- Kinomics toolbox-A web platform for analysis and viewing of kinomic peptide array data.PloS one · 2018Article
- STAT3 Induces Immunosuppression by Upregulating PD-1/PD-L1 in HNSCC.Journal of dental research · 2017Article
- Characterization of key transcription factors as molecular signatures of HPV-positive and HPV-negative oral cancers.Cancer medicine · 2017Article
- MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines.Oncology letters · 2017Article
- Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients.Carcinogenesis · 2017Article
- Biological Features of Human Papillomavirus-related Head and Neck Cancers Contributing to Improved Response.Clinical oncology (Royal College of Radiologists (Great Britain)) · 2016Article
- The Effector Domain of MARCKS Is a Nuclear Localization Signal that Regulates Cellular PIP2 Levels and Nuclear PIP2 Localization.PloS one · 2015Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A large body of evidence shows that p16(INK4a) overexpression predicts improved survival and increased radiosensitivity in HPV-mediated oropharyngeal squamous cell carcinomas.(OPSCC). Here we demonstrate that the presence of transcriptionally active HPV16 in oral cavity squamous cell carcinomas does not correlate with p16(INK4a) overexpression, enhanced local tumor immunity, or improved outcome. It is interesting that HPV-mediated oropharyngeal squamous cell carcinomas can be categorized as having a 'nonaggressive' invasion phenotype, whereas aggressive invasion phenotypes are more common in HPV-negative squamous cell carcinomas. We have developed primary cancer cell lines from resections with known pattern of invasion as determined by our validated risk model. Given that cell lines derived from HPV-mediated oropharyngeal squamous cell carcinomas are less invasive than their HPV-negative counterparts, we tested the hypothesis that viral oncoproteins E6, E7, and p16(INK4a) can affect tumor invasion. Here we demonstrate that p16(INK4a) overexpression in two cancer cell lines (UAB-3 and UAB-4), derived from oral cavity squamous cell carcinomas with the most aggressive invasive phenotype (worst pattern of invasion type 5 (WPOI-5)), dramatically decreases tumor invasiveness by altering expression of extracellular matrix remodeling genes. Pathway analysis integrating changes in RNA expression and kinase activities reveals different potential p16(INK4a)-sensitive pathways. Overexpressing p16(INK4a) in UAB-3 increases EGFR activity and increases MMP1 and MMP3 expression, possibly through STAT3 activation. Overexpressing p16(INK4a) in UAB-4 decreases PDGFR gene expression and reduces MMP1 and MMP3, possibly through STAT3 inactivation. Alternatively, ZAP70/Syk might increase MUC1 phosphorylation, leading to the observed decreased MMP1 expression.
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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.