ArticleCell death & disease2013
Wnt activation promotes neuronal differentiation of glioblastoma.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers, 2 of them syntheses that pooled it.
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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
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Glioblastoma research on zebrafish xenograft models: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Pooled it
- Pooled it
- Hypoxia inducible factor-1α-driven signaling networks regulating adult neurogenesis via Notch, Wnt, and MAPK pathways.Molecular biology reports · 2026Review
- Matrix stress relaxation promotes glioblastoma cell migration in a ligand-specific manner.Scientific reports · 2026Article
- Modulation of Wnt/β-Catenin Pathway by Aesculus hippocastanum Extract Enhances Temozolomide Sensitivity in Glioblastoma Cells.Journal of cellular and molecular medicine · 2026Article
- Review
- Tumor Innervation: From Bystander to Emerging Therapeutic Target for Cancer.International journal of molecular sciences · 2025Review
- Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies.Molecular cancer · 2025Review
- Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.Life (Basel, Switzerland) · 2025Review
- Reprogramming Glioblastoma Cells into Non-Cancerous Neuronal Cells as a Novel Anti-Cancer Strategy.Cells · 2024Article
- Speeding up Glioblastoma Cancer Research: Highlighting the Zebrafish Xenograft Model.International journal of molecular sciences · 2024Review
- DNA Damage-Induced Apoptosis Suppressor Triggers Progression and Stemness of Glioma by Enhancing Lymphoid Enhancer-Binding Factor 1 Expression.World journal of oncology · 2024Article
- Article
- FOXO1 promotes the expression of canonical WNT target genes in examined basal-like breast and glioblastoma multiforme cancer cells.FEBS open bio · 2023Article
- Review
- Molecular pathogenesis of desmoid tumor and the role of γ-secretase inhibition.NPJ precision oncology · 2022Review
- Zebrafish Models of Paediatric Brain Tumours.International journal of molecular sciences · 2022Review
- Implementation of a combined CDK inhibition and arginine-deprivation approach to target arginine-auxotrophic glioblastoma multiforme cells.Cell death & disease · 2022Article
- Signaling pathways and therapeutic approaches in glioblastoma multiforme (Review).International journal of oncology · 2022Review
- Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the biggest challenges in tumour research is the possibility to reprogram cancer cells towards less aggressive phenotypes. In this study, we reprogrammed primary Glioblastoma multiforme (GBM)-derived cells towards a more differentiated and less oncogenic phenotype by activating the Wnt pathway in a hypoxic microenvironment. Hypoxia usually correlates with malignant behaviours in cancer cells, but it has been recently involved, together with Wnt signalling, in the differentiation of embryonic and neural stem cells. Here, we demonstrate that treatment with Wnt ligands, or overexpression of β-catenin, mediate neuronal differentiation and halt proliferation in primary GBM cells. An hypoxic environment cooperates with Wnt-induced differentiation, in line with our finding that hypoxia inducible factor-1α (HIF-1α) is instrumental and required to sustain the expression of β-catenin transcriptional partners TCF-1 and LEF-1. In addition, we also found that Wnt-induced GBM cell differentiation inhibits Notch signalling, and thus gain of Wnt and loss of Notch cooperate in the activation of a pro-neuronal differentiation program. Intriguingly, the GBM sub-population enriched of cancer stem cells (CD133(+) fraction) is the primary target of the pro-differentiating effects mediated by the crosstalk between HIF-1α, Wnt, and Notch signalling. By using zebrafish transgenics and mutants as model systems to visualize and manipulate in vivo the Wnt pathway, we confirm that Wnt pathway activation is able to promote neuronal differentiation and inhibit Notch signalling of primary human GBM cells also in this in vivo set-up. In conclusion, these findings shed light on an unsuspected crosstalk between hypoxia, Wnt and Notch signalling in GBM, and suggest the potential to manipulate these microenvironmental signals to blunt GBM malignancy.
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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.