Evidence map›Paper›PMID 26527802›Full record

ArticleThe Journal of experimental medicine2015

Elp3 drives Wnt-dependent tumor initiation and regeneration in the intestine.

Aurélie Ladang, Francesca Rapino, Lukas C Heukamp, Lars Tharun, Kateryna Shostak, Damien Hermand, Sylvain Delaunay, Iva Klevernic, Zheshen Jiang, Nicolas Jacques and 10 more

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

Article in The Journal of experimental medicine, 2015. 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 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
3.7field-weighted citation impact, top 5% 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

58 citing papers in PubMed, 92 citations in OpenAlex.

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  17. ELP3 stabilizes c-Myc to promote tumorigenesis.Journal of molecular cell biology · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 3 countries.

Aurélie LadangInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Medical Chemistry, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Francesca RapinoInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Cancer Signaling, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Lukas C HeukampInstitut für Pathologie, University Hospital Cologne, 50937 Cologne, Germany.
Lars TharunInstitut für Pathologie, University Hospital Cologne, 50937 Cologne, Germany.
Kateryna ShostakInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Medical Chemistry, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Damien HermandUnité de Recherche en Physiologie Moléculaire-Laboratoire de Génétique Moléculaire, University of Namur, 5000 Namur, Belgium.
Sylvain DelaunayInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Cancer Signaling, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Iva KlevernicInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Medical Chemistry, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Zheshen JiangInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Medical Chemistry, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Nicolas JacquesInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Medical Chemistry, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Diane JamartInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Cancer Signaling, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Valérie MigeotUnité de Recherche en Physiologie Moléculaire-Laboratoire de Génétique Moléculaire, University of Namur, 5000 Namur, Belgium.
Alexandra FlorinInstitut für Pathologie, University Hospital Cologne, 50937 Cologne, Germany.
Serkan GöktunaInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Medical Chemistry, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium.
Brigitte MalgrangeInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium GIGA Neurosciences, University of Liège, 4000 Liège, Belgium.
Owen J SansomCancer Research UK Beatson Institute, Glasgow G61 1BD, Scotland, UK.
Laurent NguyenInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium GIGA Neurosciences, University of Liège, 4000 Liège, Belgium Walloon Excellence in Life Sciences and Biotechnology, 1300 Wavre, Belgium.
Reinhard BüttnerInstitut für Pathologie, University Hospital Cologne, 50937 Cologne, Germany.
Pierre CloseInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Cancer Signaling, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium pierre.close@ulg.ac.be alain.chariot@ulg.ac.be.
Alain ChariotInterdisciplinary Cluster for Applied Genoproteomics, University of Liège, 4000 Liège, Belgium Laboratory of Medical Chemistry, University of Liège, 4000 Liège, Belgium GIGA-Signal Transduction, University of Liège, 4000 Liège, Belgium Walloon Excellence in Life Sciences and Biotechnology, 1300 Wavre, Belgium pierre.close@ulg.ac.be alain.chariot@ulg.ac.be.
University of Liège · BEUniversity Hospital Cologne · DEUniversity of Namur · BEWalloon Excellence in Lifesciences and Biotechnology · BECancer Research UK Scotland Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor initiation in the intestine can rapidly occur from Lgr5(+) crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer stem cells. Here, we show that Elp3, the catalytic subunit of the Elongator complex, is required for Wnt-driven intestinal tumor initiation and radiation-induced regeneration by maintaining a subpool of Lgr5(+)/Dclk1(+)/Sox9(+) cells. Elp3 deficiency dramatically delayed tumor appearance in Apc-mutated intestinal epithelia and greatly prolonged mice survival without affecting the normal epithelium. Specific ablation of Elp3 in Lgr5(+) cells resulted in marked reduction of polyp formation upon Apc inactivation, in part due to a decreased number of Lgr5(+)/Dclk1(+)/Sox9(+) cells. Mechanistically, Elp3 is induced by Wnt signaling and promotes Sox9 translation, which is needed to maintain the subpool of Lgr5(+)/Dclk1(+) cancer stem cells. Consequently, Elp3 or Sox9 depletion led to similar defects in Dclk1(+) cancer stem cells in ex vivo organoids. Finally, Elp3 deficiency strongly impaired radiation-induced intestinal regeneration, in part because of decreased Sox9 protein levels. Together, our data demonstrate the crucial role of Elp3 in maintaining a subpopulation of Lgr5-derived and Sox9-expressing cells needed to trigger Wnt-driven tumor initiation in the intestine.

Indexed as

Adenomatous Polyposis Coli ProteinAnimalsBlotting, WesternCell Line, TumorDoublecortin-Like KinasesGene ExpressionHCT116 CellsHEK293 CellsHistone AcetyltransferasesHT29 CellsHumansIntestinal MucosaIntestinesMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutAdenomatous Polyposis Coli ProteinDclk1 protein, mouseDoublecortin-Like KinasesELP3 protein, humanElp3 protein, mouseHistone AcetyltransferasesLgr5 protein, mouseNerve Tissue ProteinsProtein Serine-Threonine KinasesReceptors, G-Protein-CoupledSox9 protein, mouseSOX9 Transcription FactorWnt Proteins

Identifiers

PMID26527802
PMCPMC4647259
OpenAlexW2178495626

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.