Evidence map›Paper›PMID 26904939›Full record

ArticleCell reports2016

Insertional Mutagenesis Identifies a STAT3/Arid1b/β-catenin Pathway Driving Neurofibroma Initiation.

Jianqiang Wu, Vincent W Keng, Deanna M Patmore, Jed J Kendall, Ami V Patel, Edwin Jousma, Walter J Jessen, Kwangmin Choi, Barbara R Tschida, Kevin A T Silverstein and 13 more

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

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

43 citing papers in PubMed, 59 citations in OpenAlex.

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  11. Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  12. Review
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  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. AfterNeuro-oncology advances · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 9 institutions in 1 country.

Jianqiang WuDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Vincent W KengMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Deanna M PatmoreDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Jed J KendallDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Ami V PatelDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Edwin JousmaDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Walter J JessenDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Kwangmin ChoiDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Barbara R TschidaMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Kevin A T SilversteinBiostatistics and Informatics, University of Minnesota, Minneapolis, MN 55455, USA.
Danhua FanBiostatistics and Informatics, University of Minnesota, Minneapolis, MN 55455, USA.
Eric B SchwartzOhio State University, College of Pharmacy, Columbus, OH 43210, USA.
James R FuchsOhio State University, College of Pharmacy, Columbus, OH 43210, USA.
Yuanshu ZouDivision of Biostatistics and Epidemiology, Cincinnati Children's Hospital Research Foundation, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Mi-Ok KimDivision of Biostatistics and Epidemiology, Cincinnati Children's Hospital Research Foundation, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Eva DombiPediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
David E LevyDepartment of Pathology and New York University Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Gang HuangDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA.
Jose A CancelasDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA; Hoxworth Blood Center, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
Anat O Stemmer-RachamimovDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Robert J SpinnerDepartment of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
David A LargaespadaMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Nancy RatnerDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA. Electronic address: nancy.ratner@cchmc.org.
Cincinnati Children's Hospital Medical Center · USUniversity of Cincinnati · USUniversity of Minnesota · USThe Ohio State University · USUniversity of Minnesota Medical Center · USHarvard University · USMayo Clinic in Florida · USNational Cancer Institute · USNew York University · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
MITOGENIC ACTIVITIES IN NEUROFIBROMATOSISR01NS028840 · NINDS · UNIVERSITY OF CINCINNATI · PI NANCY RATNER · 1990 to 2026
$10.1M
Xenograft Core for NF1 Experimental TherapeuticsP50NS057531 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI RATNER, NANCY · 2008 to 2012
$6.8M
Sleeping Beauty for uncovering cancer genes in miceR01CA113636 · NCI · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW · 2006 to 2016
$2.5M
Disordered Regulation of Wnt/beta-catenin Signaling in MPNST Development and MaintenanceR01NS086219 · NINDS · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW, RATNER, NANCY · 2014 to 2018
$2.4M
NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA113636NINDS NIH HHS NIH P50 NS057531NINDS NIH HHS NIH R01 NS28840NINDS NIH HHS P50 NS057531NINDS NIH HHS R01 NS028840NINDS NIH HHS R01 NS086219
6 · The paper itself

Abstract

To identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1) neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, and molecular analyses. We mapped an Nf1-Stat3-Arid1b/β-catenin pathway that becomes active in the context of Nf1 loss. Genetic deletion of Stat3 in Schwann cell progenitors (SCPs) and Schwann cells (SCs) prevents neurofibroma formation, decreasing SCP self-renewal and β-catenin activity. β-catenin expression rescues effects of Stat3 loss in SCPs. Importantly, P-STAT3 and β-catenin expression correlate in human neurofibromas. Mechanistically, P-Stat3 represses Gsk3β and the SWI/SNF gene Arid1b to increase β-catenin. Knockdown of Arid1b or Gsk3β in Stat3(fl/fl);Nf1(fl/fl);DhhCre SCPs rescues neurofibroma formation after in vivo transplantation. Stat3 represses Arid1b through histone modification in a Brg1-dependent manner, indicating that epigenetic modification plays a role in early tumorigenesis. Our data map a neural tumorigenesis pathway and support testing JAK/STAT and Wnt/β-catenin pathway inhibitors in neurofibroma therapeutic trials.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsbeta CateninCarcinogenesisDisease Models, AnimalDNA-Binding ProteinsDNA HelicasesFemaleGlycogen Synthase Kinase 3 betaHistonesHumansMiceMice, NudeMutagenesis, InsertionalNeoplasm TransplantationNeural Stem Cellsbeta CateninCTNNB1 protein, mouseDNA-Binding ProteinsDNA HelicasesGlycogen Synthase Kinase 3 betaHistonesNaa11 protein, mouseNeurofibromin 1N-Terminal Acetyltransferase ANuclear ProteinsRNA, Small InterferingSmarca4 protein, mouseStat3 protein, mouseSTAT3 Transcription FactorTranscription Factors

Identifiers

PMID26904939
PMCPMC4782770
OpenAlexW2276544418

What OpenQuestion holds

Textmetadata
LicenceTDM
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.