ArticlePloS one2015
Molecular and in vivo characterization of cancer-propagating cells derived from MYCN-dependent medulloblastoma.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- LOXL1-AS1 contributes to metastasis in sonic-hedgehog medulloblastoma by promoting cancer stem-like phenotypes.Journal of experimental & clinical cancer research : CR · 2024Article
- Glioma Stem Cells in Pediatric High-Grade Gliomas: From Current Knowledge to Future Perspectives.Cancers · 2022Review
- Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives.Cancers · 2021Review
- Systems pharmacogenomics identifies novel targets and clinically actionable therapeutics for medulloblastoma.Genome medicine · 2021Article
- Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead.Frontiers in oncology · 2021Review
- Targeting MYCN in Molecularly Defined Malignant Brain Tumors.Frontiers in oncology · 2020Review
- The Non-coding Side of Medulloblastoma.Frontiers in cell and developmental biology · 2020Review
- Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- The MYCN Protein in Health and Disease.Genes · 2017Review
- Review
- Medulloblastoma stem cells: Promising targets in medulloblastoma therapy.Cancer science · 2016Review
- Effects of Lovastatin on Brain Cancer Cells.Cell transplantationReview
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. While the pathways that are deregulated in MB remain to be fully characterized, amplification and/or overexpression of the MYCN gene, which is has a critical role in cerebellar development as a regulator of neural progenitor cell fate, has been identified in several MB subgroups. Phenotypically, aberrant expression of MYCN is associated with the large-cell/anaplastic MB variant, which accounts for 5-15% of cases and is associated with aggressive disease and poor clinical outcome. To better understand the role of MYCN in MB in vitro and in vivo and to aid the development of MYCN-targeted therapeutics we established tumor-derived neurosphere cell lines from the GTML (Glt1-tTA/TRE-MYCN-Luc) genetically engineered mouse model. A fraction of GTML neurospheres were found to be growth factor independent, expressed CD133 (a marker of neural stem cells), failed to differentiate upon MYCN withdrawal and were highly tumorigenic when orthotopically implanted into the cerebellum. Principal component analyzes using single cell RNA assay data suggested that the clinical candidate aurora-A kinase inhibitor MLN8237 converts GTML neurospheres to resemble non-MYCN expressors. Correlating with this, MLN8237 significantly extended the survival of mice bearing GTML MB allografts. In summary, our results demonstrate that MYCN plays a critical role in expansion and survival of aggressive MB-propagating cells, and establish GTML neurospheres as an important resource for the development of novel therapeutic strategies.
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