ArticleBreast cancer research : BCR2004
Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells.
Article in Breast cancer research : BCR, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 374 papers, 1 of them a synthesis that pooled it.
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Who cites it
374 citing papers in PubMed, 1 synthesis or guideline pooled it, 746 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
- Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study.PloS one · 2015Trial
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- The Glyco-Switch of life: O-GlcNAcylation in cell fate decision.Glycobiology · 2025Review
- Role of Notch gene receptors as prognostic biomarkers in colorectal cancer.Scientific reports · 2025Article
- The Gene Expression Profile of Milk Somatic Cells of Small Ruminant Lentivirus-Seropositive and -Seronegative Dairy Goats (Viruses · 2025Article
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- Drug Treatment Direction Based on the Molecular Mechanism of Breast Cancer Brain Metastasis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.Life (Basel, Switzerland) · 2025Review
- Mutanobactin-D, aInternational journal of molecular sciences · 2025Article
- Breast Morphogenesis: From Normal Development to Cancer.Advances in experimental medicine and biology · 2025Review
- Interactions between hedgehog signaling pathway and the complex tumor microenvironment in breast cancer: current knowledge and therapeutic promises.Cell communication and signaling : CCS · 2024Review
- Somatic mutational landscape across Indian breast cancer cases by whole exome sequencing.Scientific reports · 2024Article
- Cell-cell communication: new insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- Novel Anti-Cancer Stem Cell Compounds: A Comprehensive Review.Pharmaceutics · 2024Review
- Salivary Gland Tissue Recombination Can Modify Cell Fate.Journal of dental research · 2024Article
- Single-Cell Analysis Identifies NOTCH3-Mediated Interactions between Stromal Cells That Promote Microenvironment Remodeling and Invasion in Lung Adenocarcinoma.Cancer research · 2024Article
- Low-Dose Sorafenib Promotes Cancer Stem Cell Expansion and Accelerated Tumor Progression in Soft Tissue Sarcomas.International journal of molecular sciences · 2024Article
- FBP1 inhibits NSCLC stemness by promoting ubiquitination of Notch1 intracellular domain and accelerating degradation.Cellular and molecular life sciences : CMLS · 2024Article
- Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2024Review
314 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
introductionNotch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors.
methodsIn order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists.
resultsUtilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells.
conclusionThese studies suggest that Notch signaling plays a critical role in normal human mammary development by acting on both stem cells and progenitor cells, affecting self-renewal and lineage-specific differentiation. Based on these findings we propose that abnormal Notch signaling may contribute to mammary carcinogenesis by deregulating the self-renewal of normal mammary stem cells.
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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.