ArticleCarcinogenesis2013
The molecular features of tongue epithelium treated with the carcinogen 4-nitroquinoline-1-oxide and alcohol as a model for HNSCC.
Article in Carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Revisit of an unanswered question by pooled analysis of eight cohort studies in Japan: Does cigarette smoking and alcohol drinking have interaction for the risk of esophageal cancer?Cancer medicine · 2019Pooled it
- Vendor-specific microbiomes influence oral cancer development and its response toJournal of oral microbiology · 2026Article
- Key Early Changes in Oral Squamous Cell Carcinogenesis Are Accelerated by Ectopic BMI1 Expression.Cancer research communications · 2026Article
- Sex-Related Differences in Histone Acetylation and Tumor Development in a 4-Nitroquinoline 1-Oxide and Ethanol-Induced Oral Squamous Cell Carcinoma Mouse Model.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2025Article
- Exogenous BMI1 expression aggravates oral squamous cell carcinomas in tongue epithelia.Neoplasia (New York, N.Y.) · 2025Article
- Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy.Cancer cell · 2025Review
- Efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin or nedaplatin plus tegafur/gimeracil/oteracil as induction chemotherapy regimen for hypopharyngeal cancer.Frontiers in oncology · 2025Article
- Connecting the dots: investigating the link between environmental, genetic, and epigenetic influences in metabolomic alterations in oral squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2024Review
- The transcription factor BMI1 increases hypoxic signaling in oral cavity epithelia.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.Carcinogenesis · 2024Article
- Isolation of tumor stem-like cells from primary laryngeal squamous cell carcinoma cells (FD-LS-6).Human cell · 2024Article
- β-catenin/CBP activation of mTORC1 signaling promotes partial epithelial-mesenchymal states in head and neck cancer.Translational research : the journal of laboratory and clinical medicine · 2023Article
- Chronic Alcohol Exposure Promotes Cancer Stemness and Glycolysis in Oral/Oropharyngeal Squamous Cell Carcinoma Cell Lines by Activating NFAT Signaling.International journal of molecular sciences · 2022Article
- Fat and exposure to 4-nitroquinoline-1-oxide causes histologic and inflammatory changes in murine livers.PloS one · 2022Article
- A retinoic acid receptor β2 agonist attenuates transcriptome and metabolome changes underlying nonalcohol-associated fatty liver disease.The Journal of biological chemistry · 2021Article
- Characterization of normal and cancer stem-like cell populations in murine lingual epithelial organoids using single-cell RNA sequencing.Scientific reports · 2021Article
- Review
- Article
- Alcohol drinking inhibits NOTCH-PAX9 signaling in esophageal squamous epithelial cells.The Journal of pathology · 2021Article
- The Effect of Ethanol Consumption on Composition and Morphology of Femur Cortical Bone in Wild-Type and ALDH2*2-Homozygous Mice.Calcified tissue international · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer affecting humans worldwide. To determine the potential mechanisms by which chronic tobacco and alcohol abuse lead to HNSCC of the oral cavity, we have used both the 4-nitroquinoline-1-oxide (4-NQO) murine oral carcinogenesis and the Meadows-Cook alcohol models. In this study, we treated mice with 4-NQO in drinking water for 10 weeks and then administered 20% (w:v) ethanol (EtOH) for another 10 weeks. We observed increased levels and/or activation of signaling proteins [p38 mitogen-activated protein kinase (MAPK), β-catenin and Erk 1/2] that are typically altered during HNSCC initiation in humans. We found that EtOH administration alone increased the expression of p38 MAPK but not Erk 1/2 MAPK. Total β-catenin levels in the tongues increased by 2- to 3-fold after 4-NQO treatment, with or without EtOH. However, EtOH combined with 4-NQO reduced phosphorylated β-catenin levels, whereas 4-NQO treatment alone did not. These data implicate EtOH as a regulator of β-catenin signaling in this HNSCC model. We also utilized K14-CreER(TAM); ROSA26 mice to mark permanently stem/progenitor cells in the tongue epithelia. We found that 4-NQO alone and 4-NQO plus EtOH treatment resulted in massive, horizontal expansion of stem/progenitor cell populations arising from single stem cells in the basal layer of the epithelia. This expansion is consistent with carcinogen-associated, symmetric division of stem/progenitor cells. Our data suggest that specific therapeutic targets for prevention of HNSCC of the oral cavity associated with both alcohol and tobacco use are p38 MAPK and β-catenin.
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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.