ArticleThe Journal of cell biology2015
The Numb/p53 circuitry couples replicative self-renewal and tumor suppression in mammary epithelial cells.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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.
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Who cites it
48 citing papers in PubMed, 69 citations in OpenAlex.
- CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.Nature communications · 2022Trial
- Endocytic Control of Cell-Autonomous and Non-Cell-Autonomous Functions of p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FOXM1 Signaling Network Transcriptionally Upregulates Expression of Proteins Involved in Mitotic Progression to Induce High Proliferation and Chromosomal Instability in Androgen Receptor-Low Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- Article
- BRCA1: An Unrecognized Modulator of Lineage Plasticity in Basal-like Breast Cancer.Journal of mammary gland biology and neoplasia · 2025Review
- The CRL7Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Latest News from the "Guardian": p53 Directly Activates Asymmetric Stem Cell Division Regulators.International journal of molecular sciences · 2025Article
- Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis.Nature communications · 2024Article
- Article
- Single-Cell RNA Sequencing: Technological Progress and Biomedical Application in Cancer Research.Molecular biotechnology · 2024Review
- Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets.Signal transduction and targeted therapy · 2024Review
- p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response.Nature communications · 2023Article
- Review
- UBE2S and UBE2C confer a poor prognosis to breast cancerFrontiers in oncology · 2023Article
- Aberrant phosphorylation inactivates Numb in breast cancer causing expansion of the stem cell pool.The Journal of cell biology · 2022Article
- Aberrant activation of p53/p66Shc-mInsc axis increases asymmetric divisions and attenuates proliferation of aged mammary stem cells.Cell death and differentiation · 2022Article
- Cellular and molecular mechanisms of plasticity in cancer.Trends in cancer · 2022Review
- Numb exon 9 inclusion regulates Integrinβ5 surface expression and promotes breast cancer metastasis.Oncogene · 2022Article
- Asymmetric Cell Division and Tumor Heterogeneity.Frontiers in cell and developmental biology · 2022Review
- The role of NUMB/NUMB isoforms in cancer stem cells.BMB reports · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cell fate determinant Numb orchestrates tissue morphogenesis and patterning in developmental systems. In the human mammary gland, Numb is a tumor suppressor and regulates p53 levels. However, whether this function is linked to its role in fate determination remains unclear. Here, by exploiting an ex vivo system, we show that at mitosis of purified mammary stem cells (SCs), Numb ensures the asymmetric outcome of self-renewing divisions by partitioning into the progeny that retains the SC identity, where it sustains high p53 activity. Numb also controls progenitor maturation. At this level, Numb loss associates with the epithelial-to-mesenchymal transition and results in differentiation defects and reacquisition of stemness features. The mammary gland of Numb-knockout mice displays an expansion of the SC compartment, associated with morphological alterations and tumorigenicity in orthotopic transplants. This is because of low p53 levels and can be inhibited by restoration of Numb levels or p53 activity, which results in successful SC-targeted treatment.
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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.