ArticleThe Journal of clinical investigation2020
Norrin mediates tumor-promoting and -suppressive effects in glioblastoma via Notch and Wnt.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Non-coding RNAs in drug and radiation resistance of bone and soft-tissue sarcoma: a systematic review.eLife · 2022Pooled it
- Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Phenotypic variations in glioma stem cells: regulatory mechanisms and implications for therapeutic strategies.Journal of translational medicine · 2025Review
- Cell fate acquisition and reprogramming by the proneural transcription factor ASCL1.Open biology · 2025Review
- Importin-alpha transports Norrin to the nucleus to promote proliferation and Notch signaling in glioblastoma stem cells.Oncogene · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Norrin in cancer: from a promising prognostic biomarker to a novel therapeutic target.Frontiers in oncology · 2025Review
- Targeting glioblastoma with a brain-penetrant drug that impairs brain tumor stem cells via NLE1-Notch1 complex.Stem cell reports · 2024Article
- Effects of aflatoxin and fumonisin on gene expression of growth factors and inflammation-related genes in a human hepatocyte cell line.Mutagenesis · 2024Article
- Investigating the Impact of Dimer Interface Mutations on Norrin's Secretion and Norrin/β-Catenin Pathway Activation.Investigative ophthalmology & visual science · 2024Article
- Article
- Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma.Cells · 2022Review
- Article
- Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression.Frontiers in cell and developmental biology · 2022Review
- EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression.Cell death & disease · 2021Article
- Rosmarinic acid inhibits cell proliferation, migration, and invasion and induces apoptosis in human glioma cells.International journal of molecular medicine · 2021Article
- Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer.Frontiers in cell and developmental biology · 2021Review
- Norrin mediates opposing effects on tumor progression of glioblastoma stem cells.The Journal of clinical investigation · 2020Article
- NORRIN plays a context-dependent role in glioblastoma stem cells.Molecular & cellular oncology · 2020Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Glioblastoma multiforme (GBM) contains a subpopulation of cells, GBM stem cells (GSCs), that maintain the bulk tumor and represent a key therapeutic target. Norrin is a Wnt ligand that binds Frizzled class receptor 4 (FZD4) to activate canonical Wnt signaling. Although Norrin, encoded by NDP, has a well-described role in vascular development, its function in human tumorigenesis is largely unexplored. Here, we show that NDP expression is enriched in neurological cancers, including GBM, and its levels positively correlated with survival in a GBM subtype defined by low expression of ASCL1, a proneural factor. We investigated the function of Norrin and FZD4 in GSCs and found that it mediated opposing tumor-suppressive and -promoting effects on ASCL1lo and ASCL1hi GSCs. Consistent with a potential tumor-suppressive effect of Norrin suggested by the tumor outcome data, we found that Norrin signaling through FZD4 inhibited growth in ASCL1lo GSCs. In contrast, in ASCL1hi GSCs Norrin promoted Notch signaling, independently of WNT, to promote tumor progression. Forced ASCL1 expression reversed the tumor-suppressive effects of Norrin in ASCL1lo GSCs. Our results identify Norrin as a modulator of human brain cancer progression and reveal an unanticipated Notch-mediated function of Norrin in regulating cancer stem cell biology. This study identifies an unanticipated role of Norrin in human brain cancer progression. In addition, we provide preclinical evidence suggesting Norrin and canonical Wnt signaling as potential therapeutic targets for GBM subtype-restricted cancer 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.