ArticleMolecular oncology2018
Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Neural Cell Models of Specific Reading Disabilities: Identification of Cellular and Transcriptome Alterations.Genes, brain, and behavior · 2026Article
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- Comprehensive proteogenomic characterization reveals clinically relevant molecular subtypes associated with medulloblastoma progression.Experimental & molecular medicine · 2026Article
- Targeting TET3 suppresses group 3 medulloblastoma stemness and progression via impairing hypomethylation of Otx2 super-enhancer.Cell reports. Medicine · 2025Article
- Machine learning identification of molecular targets for medulloblastoma subgroups using microarray gene fingerprint analysis.Computational and structural biotechnology journal · 2025Article
- A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing.Nature cell biology · 2024Article
- TheInternational journal of molecular sciences · 2024Article
- Review
- Review
- Dissecting super-enhancer driven transcriptional dependencies reveals novel therapeutic strategies and targets for group 3 subtype medulloblastoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Article
- Role of MicroRNAs in the Development and Progression of the Four Medulloblastoma Subgroups.Cancers · 2021Review
- Integrated computational analyses reveal novel insights into the stromal microenvironment of SHH-subtype medulloblastoma.Scientific reports · 2021Article
- Semaphorin Regulation by the Chromatin Remodeler CHD7: An Emerging Genetic Interaction Shaping Neural Cells and Neural Crest in Development and Cancer.Frontiers in cell and developmental biology · 2021Review
- An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate.Nature communications · 2020Article
- Modeling medulloblastoma in vivo and with human cerebellar organoids.Nature communications · 2020Article
- Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors.Medical sciences (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet we know the least about the molecular mechanisms driving their progression. Here, we show that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self-renewal while inhibiting differentiation in vitro and increases tumor initiation from MB stem/progenitor cells in vivo. To determine how OTX2 contributes to these processes, we employed complementary bioinformatic approaches to characterize the OTX2 regulatory network and identified novel relationships between OTX2 and genes associated with neuronal differentiation and axon guidance signaling in Group 3 and Group 4 MB stem/progenitor cells. In particular, OTX2 levels were negatively correlated with semaphorin (SEMA) signaling, as expression of 9 SEMA pathway genes is upregulated following OTX2 knockdown with some being potential direct OTX2 targets. Importantly, this negative correlation was also observed in patient samples, with lower expression of SEMA4D associated with poor outcome specifically in Group 4 tumors. Functional proof-of-principle studies demonstrated that increased levels of select SEMA pathway genes are associated with decreased self-renewal and growth in vitro and in vivo and that RHO signaling, known to mediate the effects of SEMA genes, is contributing to the OTX2 KD phenotype. Our study provides mechanistic insight into the networks controlled by OTX2 in MB stem/progenitor cells and reveals novel roles for axon guidance genes and their downstream effectors as putative tumor suppressors in MB.
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Registered trials
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