Evidence map›Paper›PMID 31811703›Full record

ArticleMolecular oncology2020

Focal adhesion kinase confers pro-migratory and antiapoptotic properties and is a potential therapeutic target in Ewing sarcoma.

Konrad Steinestel, Marcel Trautmann, Esther-Pia Jansen, Uta Dirksen, Jan Rehkämper, Jan-Henrik Mikesch, Julia S Gerke, Martin F Orth, Giuseppina Sannino, Maria-Francisca Arteaga and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

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  10. New Insights on the Nuclear Functions and Targeting of FAK in Cancer.International journal of molecular sciences · 2022
    Review
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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

14 authors at 5 institutions in 2 countries.

Konrad SteinestelGerhard Domagk Institute of Pathology, University Hospital Münster, Germany.ORCID 0000-0002-6549-9848
Marcel TrautmannGerhard Domagk Institute of Pathology, University Hospital Münster, Germany.ORCID 0000-0002-5842-1196
Esther-Pia JansenGerhard Domagk Institute of Pathology, University Hospital Münster, Germany.
Uta DirksenPediatrics III, West German Cancer Centre, University Hospital Essen, Germany.
Jan RehkämperInstitute of Pathology, University Hospital Cologne, Germany.
Jan-Henrik MikeschDepartment of Medicine A, University Hospital Münster, Germany.
Julia S GerkeMax Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Germany.
Martin F OrthMax Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Germany.
Giuseppina SanninoMax Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Germany.
Maria-Francisca ArteagaDepartment of Medicine A, University Hospital Münster, Germany.
Claudia RossigDepartment of Pediatric Hematology and Oncology, University Children's Hospital Münster, Germany.
Eva WardelmannGerhard Domagk Institute of Pathology, University Hospital Münster, Germany.
Thomas G P GrünewaldMax Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Germany.
Wolfgang HartmannGerhard Domagk Institute of Pathology, University Hospital Münster, Germany.
University Hospital Münster · DEMax Planck Institute of Psychiatry · DEGerman Cancer Research Center · DEUniversity Hospital Cologne · DEWest Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oncogenesis of Ewing sarcoma (EwS), the second most common malignant bone tumor of childhood and adolescence, is dependent on the expression of chimeric EWSR1-ETS fusion oncogenes, most often EWSR1-FLI1 (E/F). E/F expression leads to dysregulation of focal adhesions (FAs) enhancing the migratory capacity of EwS cells. Here, we show that, in EwS cell lines and tissue samples, focal adhesion kinase (FAK) is expressed and phosphorylated at Y397 in an E/F-dependent way involving Ezrin. Employing different EwS cell lines as in vitro models, we found that key malignant properties of E/F are mediated via substrate-independent autophosphorylation of FAK on Y397. This phosphorylation results in enhanced FA formation, Rho-dependent cell migration, and impaired caspase-3-mediated apoptosis in vitro. Conversely, treatment with the FAK inhibitor 15 (1,2,4,5-benzenetetraamine tetrahydrochloride (Y15) enhanced caspase-mediated apoptosis and EwS cell migration, independent from the respective EWSR1-ETS fusion type, mimicking an anoikis-like phenotype and paralleling the effects of FAK siRNA knockdown. Our findings were confirmed in vivo using an avian chorioallantoic membrane model and provide a first rationale for the therapeutic use of FAK inhibitors to impair metastatic dissemination of EwS.

Indexed as

Aniline CompoundsAnimalsApoptosisBone NeoplasmsCaspase 3Cell Line, TumorCell MovementCell SurvivalChick EmbryoChildCytoskeletal ProteinsEzrinFocal Adhesion Protein-Tyrosine KinasesFocal AdhesionsGene Knockdown TechniquesHumans1,2,4,5-benzenetetraamineAniline CompoundsCASP3 protein, humanCaspase 3Cytoskeletal ProteinsEWSR1 protein, humanEzrinFocal Adhesion Protein-Tyrosine KinasesOncogene Proteins, FusionProto-Oncogene Proteins c-etsRNA-Binding Protein EWSRNA, Small InterferingcytoskeletonEwing sarcomafocal adhesion kinasemetastasismigration

Identifiers

PMID31811703
PMCPMC6998388
OpenAlexW2993624530

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.