Evidence map›Paper›PMID 25453903›Full record

ArticleCancer cell2014

EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma.

Nicolò Riggi, Birgit Knoechel, Shawn M Gillespie, Esther Rheinbay, Gaylor Boulay, Mario L Suvà, Nikki E Rossetti, Wannaporn E Boonseng, Ozgur Oksuz, Edward B Cook and 12 more

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

Article in Cancer cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 309 papers.

0numbers the graph read from it
0cells of the map it votes in
309citing papers in PubMed
19.8field-weighted citation impact, top 1% 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

309 citing papers in PubMed, 461 citations in OpenAlex.

  1. Trial
  2. Article
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  4. A Drosophila Study Model for EWS::FLI1-Induced Molecular Pathways.Methods in molecular biology (Clifton, N.J.) · 2027
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  15. Review
  16. STAG2 loss amplifies EWS-FLI1-driven microsatellite enhancer activity promoting Ewing sarcoma aggressiveness.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  17. Article
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249 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 8 institutions in 2 countries.

Nicolò Riggi *Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Birgit Knoechel *Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Shawn M Gillespie *Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Esther RheinbayDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Gaylor BoulayDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Mario L SuvàDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nikki E RossettiDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Wannaporn E BoonsengDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ozgur OksuzDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Edward B CookDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Aurélie FormeyInstitute of Pathology, Centre Hospitalier Universitaire Vaudois, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Anoop PatelHoward Hughes Medical Institute, Chevy Chase, MD, USA.
Melissa GymrekWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts, USA.
Vishal ThaparCancer Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Vikram DeshpandeDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
David T TingCancer Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Francis J HornicekCenter for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
G Petur NielsenDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ivan StamenkovicInstitute of Pathology, Centre Hospitalier Universitaire Vaudois, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Martin J AryeeDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Bradley E Bernstein *Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Miguel N Rivera *Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Harvard University · USMassachusetts General Hospital · USCenter for Cancer Research · USBroad Institute · USHarvard–MIT Division of Health Sciences and Technology · USHoward Hughes Medical Institute · USUniversity Hospital of Lausanne · CHUniversity of Lausanne · CH

Funding

PATHOPHYSIOLOGY OF HUMAN BLOOD CELLST32HL007574 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Daniel Evan Bauer · 1985 to 2026
$18.4M
Dana Farber/Harvard Cancer Consortium Career Development Program in Clinical OncologyK12CA087723 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Tsai Ting · 2002 to 2026
$17.9M
High-throughput sequencing of chromatin regulatory elementsU54HG004570 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERNSTEIN, BRADLEY EVAN · 2007 to 2011
$8.1M
Expanding the catalog of chromatin regulatory elements in the human genomeU54HG006991 · NHGRI · BROAD INSTITUTE, INC. · PI BERNSTEIN, BRADLEY EVAN · 2012 to 2016
$7.9M
Howard Hughes Medical InstituteNCI NIH HHS K12 CA087723NHGRI NIH HHS U54 HG004570NHGRI NIH HHS U54 HG006991NHLBI NIH HHS T32 HL007574NHLBI NIH HHS T32 HL007574-30
6 · The paper itself

Abstract

The aberrant transcription factor EWS-FLI1 drives Ewing sarcoma, but its molecular function is not completely understood. We find that EWS-FLI1 reprograms gene regulatory circuits in Ewing sarcoma by directly inducing or repressing enhancers. At GGAA repeat elements, which lack evolutionary conservation and regulatory potential in other cell types, EWS-FLI1 multimers induce chromatin opening and create de novo enhancers that physically interact with target promoters. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors. These divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators while activating oncogenes and potential therapeutic targets, such as the kinase VRK1. Our findings demonstrate how EWS-FLI1 establishes an oncogenic regulatory program governing both tumor survival and differentiation.

Indexed as

Chromatin Assembly and DisassemblyAnimalsBase SequenceBone NeoplasmsCell Line, TumorEnhancer Elements, GeneticGene Expression Regulation, NeoplasticHumansMice, Inbred NODMice, SCIDNeoplasm TransplantationOncogene Proteins, FusionProtein BindingProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSSarcoma, EwingEWS-FLI fusion proteinOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWS

Identifiers

PMID25453903
PMCPMC4492343
OpenAlexW1971516612

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.