ArticleGenes & development2002
Specific down-modulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformation.
Article in Genes & development, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 259 citations in OpenAlex.
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- Immunohistochemical Evaluation of NOTCH1 Signaling Pathway in Oral Squamous Cell Carcinoma: Clinical and Prognostic Significance.International journal of molecular sciences · 2025Article
- Human papillomavirus genomes associate with active host chromatin during persistent viral infection.PLoS pathogens · 2025Article
- Review
- Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer.Frontiers in cell and developmental biology · 2025Review
- Pathogenesis and Management Strategies in Radioiodine-Refractory Differentiated Thyroid Cancer: From Molecular Mechanisms Toward Therapeutic Approaches: A Comprehensive Review.Journal of clinical medicine · 2024Review
- The N-acetylglucosaminyltransferase Radical fringe contributes to defects in JAG1-dependent turnover and signaling of NOTCH3 CADASIL mutants.The Journal of biological chemistry · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Circulating cell-free HPV DNA is a strong marker for disease severity in cervical cancer.Molecular oncology · 2024Article
- Role of Notch1 Signaling Pathway in Small Cell Lung Carcinoma.Iranian journal of pathology · 2024Review
- Molecular pathways and targeted therapies in head and neck cancers pathogenesis.Frontiers in oncology · 2024Review
- The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome.Nature communications · 2023Article
- Article
- p73α1, a p73 C-terminal isoform, regulates tumor suppression and the inflammatory response via Notch1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Antiproliferative and apoptotic potential of Glycyrrhizin against HPV16+ Caski cervical cancer cells: A plausible association with downreguation of HPV E6 and E7 oncogenes and Notch signaling pathway.Saudi journal of biological sciences · 2022Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Rutin Mediated Apoptotic Cell Death in Caski Cervical Cancer Cells viaLife (Basel, Switzerland) · 2021Article
- Review
- Human papillomavirus E6 and E7: What remains?Tumour virus research · 2021Review
- E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer.Cell death and differentiation · 2021Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The Notch family of cell surface receptors plays a key role in cell-fate determination and differentiation, functioning in a cell- and context-specific manner. In mammalian cells, Notch activation is generally thought to maintain stem cell potential and inhibit differentiation, thereby promoting carcinogenesis. However, in other contexts such as primary epithelial cells (keratinocytes), increased Notch activity causes exit from the cell cycle and/or commitment to differentiation. We now report that expression of the endogenous Notch1 gene is markedly reduced in a panel of cervical carcinoma cells whereas expression of Notch2 remains elevated, and Notch1 expression is similarly reduced or absent in invasive cervical cancers. Conversely, expression of activated Notch1 causes strong growth inhibition of HPV-positive, but not HPV-negative, cervical carcinoma cells, but exerts no such effects on other epithelial tumor cells. Increased Notch1 signaling, but not Notch2, causes a dramatic down-modulation of HPV-driven transcription of the E6/E7 viral genes, through suppression of AP-1 activity by up-regulation of the Fra-1 family member and decreased c-Fos expression. Thus, Notch1 exerts specific protective effects against HPV-induced transformation through suppression of E6/E7 expression, and down-modulation of Notch1 expression is likely to play an important role in late stages of HPV-induced carcinogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.