Evidence map›Paper›PMID 32686664›Full record

ArticleNature communications2020

An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate.

Jamie Zagozewski, Ghazaleh M Shahriary, Ludivine Coudière Morrison, Olivier Saulnier, Margaret Stromecki, Agnes Fresnoza, Gareth Palidwor, Christopher J Porter, Antoine Forget, Olivier Ayrault and 8 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2020. 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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 37 citations in OpenAlex.

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  10. TheInternational journal of molecular sciences · 2024
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  12. International journal of molecular sciences · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 2 countries.

Jamie ZagozewskiRegenerative Medicine Program, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
Ghazaleh M ShahriaryRegenerative Medicine Program, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.ORCID http://orcid.org/0000-0002-3393-5617
Ludivine Coudière MorrisonRegenerative Medicine Program, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
Olivier SaulnierThe Arthur and Sonia Labatt Brain Tumour Research Center, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-4111-1017
Margaret StromeckiRegenerative Medicine Program, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
Agnes FresnozaCentral Animal Care Services, University of Manitoba, Winnipeg, MB, Canada.
Gareth PalidworOttawa Bioinformatics Core Facility, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Christopher J PorterOttawa Bioinformatics Core Facility, Ottawa Hospital Research Institute, Ottawa, ON, Canada.ORCID http://orcid.org/0000-0001-8636-4515
Antoine ForgetInstitut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France.
Olivier AyraultInstitut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France.ORCID http://orcid.org/0000-0002-7942-6674
Cynthia HawkinsThe Arthur and Sonia Labatt Brain Tumour Research Center, The Hospital for Sick Children, Toronto, ON, Canada.
Jennifer A ChanDepartment of Pathology & Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
Maria C VladoiuThe Arthur and Sonia Labatt Brain Tumour Research Center, The Hospital for Sick Children, Toronto, ON, Canada.
Lakshmikirupa SundaresanThe Arthur and Sonia Labatt Brain Tumour Research Center, The Hospital for Sick Children, Toronto, ON, Canada.
Janilyn ArsenioDepartments of Internal Medicine and Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Michael D TaylorThe Arthur and Sonia Labatt Brain Tumour Research Center, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-7009-3466
Vijay RamaswamyThe Arthur and Sonia Labatt Brain Tumour Research Center, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-6557-895X
Tamra E Werbowetski-OgilvieRegenerative Medicine Program, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada. Tamra.Ogilvie@umanitoba.ca.ORCID http://orcid.org/0000-0002-5469-0559
University of Manitoba · CAUniversity of Toronto · CAHospital for Sick Children · CAOttawa Hospital · CAUniversité Paris-Sud · FRResearch Manitoba · CAUniversity of Calgary · CA

Funding

CIHR
6 · The paper itself

Abstract

OTX2 is a potent oncogene that promotes tumor growth in Group 3 medulloblastoma. However, the mechanisms by which OTX2 represses neural differentiation are not well characterized. Here, we perform extensive multiomic analyses to identify an OTX2 regulatory network that controls Group 3 medulloblastoma cell fate. OTX2 silencing modulates the repressive chromatin landscape, decreases levels of PRC2 complex genes and increases the expression of neurodevelopmental transcription factors including PAX3 and PAX6. Expression of PAX3 and PAX6 is significantly lower in Group 3 medulloblastoma patients and is correlated with reduced survival, yet only PAX3 inhibits self-renewal in vitro and increases survival in vivo. Single cell RNA sequencing of Group 3 medulloblastoma tumorspheres demonstrates expression of an undifferentiated progenitor program observed in primary tumors and characterized by translation/elongation factor genes. Identification of mTORC1 signaling as a downstream effector of OTX2-PAX3 reveals roles for protein synthesis pathways in regulating Group 3 medulloblastoma pathogenesis.

Indexed as

Cerebellar NeoplasmsMedulloblastomaAnimalsCarcinogenesisCell DifferentiationCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansNeoplastic Stem CellsOncogenesOtx Transcription FactorsPAX3 Transcription FactorPAX6 Transcription FactorSignal TransductionOTX2 protein, humanOtx Transcription FactorsPAX3 protein, humanPAX3 Transcription FactorPAX6 protein, humanPAX6 Transcription Factor

Identifiers

PMID32686664
PMCPMC7371715
OpenAlexW3042394052

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.