ArticleOncogene2017
Inhibition of WNT signaling attenuates self-renewal of SHH-subgroup medulloblastoma.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- CK1α agonists attenuate medulloblastoma stemness and relapse risk.Cell death & disease · 2026Article
- Medulloblastoma in Adolescents and Young Adults: Molecular Subgroups, Prognostic Biomarkers, and Age-Specific Therapeutic Challenges.Current issues in molecular biology · 2026Review
- Review
- A Druggable UHRF1/DNMT1/GLI Complex Regulates Sonic Hedgehog-Dependent Tumor Growth.Molecular cancer research : MCR · 2022Article
- Noncanonical activation of GLI signaling in SOX2Science advances · 2022Article
- T-Cell Factors as Transcriptional Inhibitors: Activities and Regulations in Vertebrate Head Development.Frontiers in cell and developmental biology · 2021Review
- The hedgehog pathway regulates cancer stem cells in serous adenocarcinoma of the ovary.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Dual Role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma.Nature communications · 2020Article
- Dlp-mediated Hh and Wnt signaling interdependence is critical in the niche for germline stem cell progeny differentiation.Science advances · 2020Article
- Methylation Profiling of Medulloblastoma in a Clinical Setting Permits Sub-classification and Reveals New Outcome Predictions.Frontiers in neurology · 2020Article
- Differential Expression of Genes for Ubiquitin Ligases in Medulloblastoma Subtypes.Cerebellum (London, England) · 2019Article
- A CK1α Activator Penetrates the Brain and Shows Efficacy Against Drug-resistant Metastatic Medulloblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Recent advances in SHH medulloblastoma progression: tumor suppressor mechanisms and the tumor microenvironment.F1000Research · 2019Review
- Review
- Protein arginine methyltransferase 5 regulates SHH-subgroup medulloblastoma progression.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The SMOOTHENED inhibitor vismodegib is FDA approved for advanced basal cell carcinoma (BCC), and shows promise in clinical trials for SONIC HEDGEHOG (SHH)-subgroup medulloblastoma (MB) patients. Clinical experience with BCC patients shows that continuous exposure to vismodegib is necessary to prevent tumor recurrence, suggesting the existence of a vismodegib-resistant reservoir of tumor-propagating cells. We isolated such tumor-propagating cells from a mouse model of SHH-subgroup MB and grew them as sphere cultures. These cultures were enriched for the MB progenitor marker SOX2 and formed tumors in vivo. Moreover, while their ability to self-renew was resistant to SHH inhibitors, as has been previously suggested, this self-renewal was instead WNT-dependent. We show here that loss of Trp53 activates canonical WNT signaling in these SOX2-enriched cultures. Importantly, a small molecule WNT inhibitor was able to reduce the propagation and growth of SHH-subgroup MB in vivo, in an on-target manner, leading to increased survival. Our results imply that the tumor-propagating cells driving the growth of bulk SHH-dependent MB are themselves WNT dependent. Further, our data suggest combination therapy with WNT and SHH inhibitors as a therapeutic strategy in patients with SHH-subgroup MB, in order to decrease the tumor recurrence commonly observed in patients treated with vismodegib.
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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.