ArticleClinical cancer research : an official journal of the American Association for Cancer Research2018
Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Targeting notch signaling pathway in esophageal cancer: from molecular insights to therapies.Oncology reviews · 2026Review
- Immunohistochemical Evaluation of NOTCH1 Signaling Pathway in Oral Squamous Cell Carcinoma: Clinical and Prognostic Significance.International journal of molecular sciences · 2025Article
- Review
- Pathological variants in HPV-independent vulvar tumours.Scientific reports · 2025Article
- RAB4A is a master regulator of cancer cell stemness upstream of NUMB-NOTCH signaling.Cell death & disease · 2024Article
- Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma.World journal of gastroenterology · 2024Review
- In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Oral squamous cell carcinomas: state of the field and emerging directions.International journal of oral science · 2023Review
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- Review
- Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma.Biomarker research · 2023Review
- The oncogenic role of NOTCH1 as biomarker in oral squamous cell carcinoma and oral lichen planus.Dental research journal · 2023Article
- Review
- Expanded Basal Compartment and Disrupted Barrier in Vocal Fold Epithelium Infected with Mouse Papillomavirus MmuPV1.Viruses · 2022Article
- HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management.Nature reviews. Clinical oncology · 2022Review
- FAS receptor regulates NOTCH activity through ERK-JAG1 axis activation and controls oral cancer stemness ability and pulmonary metastasis.Cell death discovery · 2022Article
- Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- Review
- The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis.Cancers · 2021Review
- Human papillomavirus E6 and E7: What remains?Tumour virus research · 2021Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
purposeHead and neck squamous cell carcinoma (HNSCC), a common cancer worldwide, is etiologically associated with tobacco use, high alcohol consumption, and high-risk human papillomaviruses (HPV). The Notch signaling pathway, which is involved in cell differentiation decisions with differential downstream targets and effects depending on tissue type and developmental stage, has been implicated in human HNSCC. EXPERIMENTAL
designTo assess the role of Notch signaling in HPV-positive and HPV-negative HNSCC, we utilized genetically engineered mouse (GEM) models for conventional keratinizing HNSCC, in which either HPV16 E6 and E7 oncoproteins or a gain-of-function mutant p53 are expressed, and in which we inactivated canonical Notch signaling via expression of a dominant negative form of MAML1 (DNMAML1), a required transcriptional coactivator of Notch signaling.
resultsLoss of canonical Notch signaling increased tumorigenesis in both contexts and also caused an increase in nuclear β-catenin, a marker for increased tumorigenic potential. When combined with loss of canonical Notch signaling, HPV oncogenes led to the highest frequency of cancers overall and the largest number of poorly differentiated (high-grade) cancers.
conclusionsThese findings inform on the contribution of loss of canonical Notch signaling in head and neck carcinogenesis.
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