ArticleStem cells (Dayton, Ohio)2012
Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity.
Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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.
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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Tracing the origins of glioblastoma by investigating the role of gliogenic and related neurogenic genes/signaling pathways in GBM development: a systematic review.World journal of surgical oncology · 2022Pooled it
- F-box proteins at the crossroads of ubiquitination and tumor immunity: regulatory networks and immunotherapy strategies.Frontiers in immunology · 2025Review
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- Inhibitors Targeting the F-BOX Proteins.Cell biochemistry and biophysics · 2023Review
- Article
- The Role of FBXW7 in Gynecologic Malignancies.Cells · 2023Review
- Review
- Clinical significance of FBXW7 loss of function in human cancers.Molecular cancer · 2022Review
- Aberrant Notch signaling in gliomas: a potential landscape of actionable converging targets for combination approach in therapies resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Molecular Mechanisms of KDELC2 on Glioblastoma Tumorigenesis and Temozolomide Resistance.Biomedicines · 2020Article
- Ehrlichia chaffeensis TRP120-mediated ubiquitination and proteasomal degradation of tumor suppressor FBW7 increases oncoprotein stability and promotes infection.PLoS pathogens · 2020Article
- FBW7 in hematological tumors.Oncology letters · 2020Review
- All-trans retinoic acid therapy induces asymmetric division of glioma stem cells from the U87MG cell line.Oncology letters · 2019Article
- HMGA1 negatively regulates NUMB expression at transcriptional and post transcriptional level in glioblastoma stem cells.Cell cycle (Georgetown, Tex.) · 2019Article
- Inadequate DNA Damage Repair Promotes Mammary Transdifferentiation, Leading to BRCA1 Breast Cancer.Cell · 2019Article
- Review
- FBXW7 in Cancer: What Has Been Unraveled Thus Far?Cancers · 2019Review
- Interactome Mapping Uncovers a General Role for Numb in Protein Kinase Regulation.Molecular & cellular proteomics : MCP · 2018Article
- Physiological functions of FBW7 in cancer and metabolism.Cellular signalling · 2018Review
- Molecular Mechanisms Governing the Stem Cell's Fate in Brain Cancer: Factors of Stemness and Quiescence.Frontiers in cellular neuroscience · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Glioblastoma contains a hierarchy of stem-like cancer cells, but how this hierarchy is established is unclear. Here, we show that asymmetric Numb localization specifies glioblastoma stem-like cell (GSC) fate in a manner that does not require Notch inhibition. Numb is asymmetrically localized to CD133-hi GSCs. The predominant Numb isoform, Numb4, decreases Notch and promotes a CD133-hi, radial glial-like phenotype. However, upregulation of a novel Numb isoform, Numb4 delta 7 (Numb4d7), increases Notch and AKT activation while nevertheless maintaining CD133-hi fate specification. Numb knockdown increases Notch and promotes growth while favoring a CD133-lo, glial progenitor-like phenotype. We report the novel finding that Numb4 (but not Numb4d7) promotes SCF(Fbw7) ubiquitin ligase assembly and activation to increase Notch degradation. However, both Numb isoforms decrease epidermal growth factor receptor (EGFR) expression, thereby regulating GSC fate. Small molecule inhibition of EGFR activity phenocopies the effect of Numb on CD133 and Pax6. Clinically, homozygous NUMB deletions and low Numb mRNA expression occur primarily in a subgroup of proneural glioblastomas. Higher Numb expression is found in classical and mesenchymal glioblastomas and correlates with decreased survival. Thus, decreased Numb promotes glioblastoma growth, but the remaining Numb establishes a phenotypically diverse stem-like cell hierarchy that increases tumor aggressiveness and therapeutic resistance.
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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.