ArticleGenes & development2007
Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases.
Article in Genes & development, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.
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Who cites it
179 citing papers in PubMed, 307 citations in OpenAlex.
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Current and Emerging Protein Biomarkers for the Diagnosis and Prognosis of Head and Neck Cancer.Genes · 2025Review
- Review
- Review
- Antimicrobial and Anticancer Activities ofNutrients · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- Clones in blood and stratified epithelial cells, and their drivers.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- The heterogeneity of NOTCH1 to tumor immune infiltration in pan-cancer.Scientific reports · 2024Article
- Cancer-associated fibroblast subtypes modulate the tumor-immune microenvironment and are associated with skin cancer malignancy.Nature communications · 2024Article
- The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review.Cancers · 2024Review
- Skin Development and Disease: A Molecular Perspective.Current issues in molecular biology · 2024Review
- Genome-wide DNA methylation profiles and breast cancer among World Trade Center survivors.Environmental epidemiology (Philadelphia, Pa.) · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- A novel search engine for proteins involved in Notch crosstalk signaling pathways.Journal of biosciences · 2024Article
- Human papillomaviruses: Knowns, mysteries, and unchartered territories.Journal of medical virology · 2023Review
- LncRNA H19 mediates BMP9-induced angiogenesis in mesenchymal stem cells by promoting the p53-Notch1 angiogenic signaling axis.Genes & diseases · 2023Article
- Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage.Nature communications · 2023Article
- High-Intensity Focused Ultrasound Decreases Subcutaneous Fat Tissue Thickness by Increasing Apoptosis and Autophagy.Biomolecules · 2023Article
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
119 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Little is known about the regulation and function of the Notch1 gene in negative control of human tumors. Here we show that Notch1 gene expression and activity are substantially down-modulated in keratinocyte cancer cell lines and tumors, with expression of this gene being under p53 control in these cells. Genetic suppression of Notch signaling in primary human keratinocytes is sufficient, together with activated ras, to cause aggressive squamous cell carcinoma formation. Similar tumor-promoting effects are also caused by in vivo treatment of mice, grafted with keratinocytes expressing oncogenic ras alone, with a pharmacological inhibitor of endogenous Notch signaling. These effects are linked with a lesser commitment of keratinocytes to differentiation, an expansion of stem cell populations, and a mechanism involving up-regulation of ROCK1/2 and MRCKalpha kinases, two key effectors of small Rho GTPases previously implicated in neoplastic progression. Thus, the Notch1 gene is a p53 target with a role in human tumor suppression through negative regulation of Rho effectors.
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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.