ArticleProceedings of the National Academy of Sciences of the United States of America2010
Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
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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.
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Who cites it
104 citing papers in PubMed, 158 citations in OpenAlex.
- Review
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- Chromosome evolution screens recapitulate tissue-specific tumor aneuploidy patterns.Nature genetics · 2024Article
- Article
- Notch-1/2 receptors and Jagged-1 ligand, but not HERP-1 transcription factor, are immunohistochemically expressed in the epithelial lining of periapical cysts.Journal of clinical and experimental dentistry · 2024Article
- Sustained Oncogenic Signaling in the Cytostatic State Enables Targeting of Nonproliferating Persistent Cancer Cells.Cancer research · 2022Article
- GIT1 protects against breast cancer growth through negative regulation of Notch.Nature communications · 2022Article
- Different Expression Levels of DLK2 Inhibit NOTCH Signaling and Inversely Modulate MDA-MB-231 Breast Cancer Tumor Growth In Vivo.International journal of molecular sciences · 2022Article
- The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions.Cancers · 2021Review
- The developmental origins of Notch-driven intrahepatic bile duct disorders.Disease models & mechanisms · 2021Article
- Gamma Secretase Inhibitors in Cancer: A Current Perspective on Clinical Performance.The oncologist · 2021Review
- Review
- Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases.Frontiers in immunology · 2021Review
- Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells.International journal of radiation biology · 2020Article
- GIRK1 triggers multiple cancer-related pathways in the benign mammary epithelial cell line MCF10A.Scientific reports · 2019Article
- Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation.Nature communications · 2019Article
- The Significance of NOTCH Pathway in the Development of Fibrosis in Systemic Sclerosis.Annals of dermatology · 2019Review
- Effects of Notch signalling on the expression of SEMA3C, HMGA2, CXCL14, CXCR7, and CCL20 in breast cancer.Turkish journal of biology = Turk biyoloji dergisi · 2019Article
- TSC1 and DEPDC5 regulate HIV-1 latency through the mTOR signaling pathway.Emerging microbes & infections · 2018Article
44 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
12 authors at 4 institutions in 1 country.
Funding
Abstract
Aberrant activation of Notch receptors has been implicated in breast cancer; however, the mechanisms contributing to Notch-dependent transformation remain elusive because Notch displays dichotomous functional activities, promoting both proliferation and growth arrest. We investigated the cellular basis for the heterogeneous responses to Notch pathway activation in 3D cultures of MCF-10A mammary epithelial cells. Expression of a constitutively active Notch-1 intracellular domain (NICD) was found to induce two distinct types of 3D structures: large, hyperproliferative structures and small, growth-arrested structures with reduced cell-to-matrix adhesion. Interestingly, we found that these heterogeneous phenotypes reflect differences in Notch pathway activation levels; high Notch activity caused down-regulation of multiple matrix-adhesion genes and inhibition of proliferation, whereas low Notch activity maintained matrix adhesion and provoked a strong hyperproliferative response. Moreover, microarray analyses implicated NICD-induced p63 down-regulation in loss of matrix adhesion. In addition, a reverse-phase protein array-based analysis and subsequent loss-of-function studies identified STAT3 as a dominant downstream mediator of the NICD-induced outgrowth. These results indicate that the phenotypic responses to Notch are determined by the dose of pathway activation; and this dose affects the balance between growth-stimulative and growth-suppressive effects. This unique feature of Notch signaling provides insights into mechanisms that contribute to the dichotomous effects of Notch during development and tumorigenesis.
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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.