Evidence map›Paper›PMID 31873172›Full record

ArticleScientific reports2019

Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone.

Ilka Isfort, Sandra Elges, Magdalene Cyra, Ruth Berthold, Marcus Renner, Gunhild Mechtersheimer, Pierre Åman, Olle Larsson, Nancy Ratner, Susanne Hafner and 9 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 36 citations in OpenAlex.

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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

19 authors at 7 institutions in 3 countries.

Ilka IsfortDivision of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.ORCID http://orcid.org/0000-0002-7485-8769
Sandra ElgesGerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.
Magdalene CyraDivision of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.ORCID http://orcid.org/0000-0001-7738-2703
Ruth BertholdDivision of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.ORCID http://orcid.org/0000-0001-7918-1657
Marcus RennerInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Gunhild MechtersheimerInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Pierre ÅmanSahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Olle LarssonDepartments of Oncology & Pathology, The Karolinska Institute, Stockholm, Sweden.
Nancy RatnerDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America.
Susanne HafnerInstitute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, Ulm, Germany.
Thomas SimmetInstitute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, Ulm, Germany.
Christoph SchliemannDepartment of Medicine A, Hematology and Oncology, Münster University Hospital, Münster, Germany.
Claudia RossigDepartment of Pediatric Hematology and Oncology, University Children´s Hospital Münster, Münster, Germany.
Uta DirksenPediatrics III, West German Cancer Center, University Hospital Essen, Essen, Germany.
Inga GrünewaldDivision of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.
Eva WardelmannGerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.
Sebastian HussGerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.
Wolfgang HartmannDivision of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany. wolfgang.hartmann@ukmuenster.de.ORCID http://orcid.org/0000-0002-7609-5021
Marcel TrautmannDivision of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany. marcel.trautmann@ukmuenster.de.ORCID http://orcid.org/0000-0002-5842-1196
University Hospital Münster · DEHeidelberg University · DEUniversität Ulm · DECincinnati Children's Hospital Medical Center · USGerman Cancer Society · DEKarolinska Institutet · SESahlgrenska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumors of soft tissue and bone represent a heterogeneous group of neoplasias characterized by a wide variety of genetic aberrations. Albeit knowledge on tumorigenesis in mesenchymal tumors is continuously increasing, specific insights on altered signaling pathways as a basis for molecularly targeted therapeutic strategies are still sparse. The aim of this study was to determine the involvement of YAP1/TAZ-mediated signals in tumors of soft tissue and bone. Expression levels of YAP1 and TAZ were analyzed by immunohistochemistry in a large cohort of 486 tumor specimens, comprising angiosarcomas (AS), Ewing sarcomas, leiomyosarcomas, malignant peripheral nerve sheath tumors (MPNST), solitary fibrous tumors, synovial sarcomas (SySa), well-differentiated/dedifferentiated/pleomorphic and myxoid liposarcomas (MLS). Moderate to strong nuclear staining of YAP1 and TAZ was detected in 53% and 33%, respectively. YAP1 nuclear expression was most prevalent in MPNST, SySa and MLS, whereas nuclear TAZ was predominately detected in AS, MLS and MPNST. In a set of sarcoma cell lines, immunoblotting confirmed nuclear localization of YAP1 and TAZ, corresponding to their transcriptionally active pool. Suppression of YAP1/TAZ-TEAD mediated transcriptional activity significantly impaired sarcoma cell viability in vitro and in vivo. Our findings identify nuclear YAP1 and TAZ positivity as a common feature in subsets of sarcomas of soft tissue and bone and provide evidence of YAP1/TAZ-TEAD signaling as a specific liability to be considered as a new target for therapeutic intervention. Nuclear YAP1/TAZ expression may represent a biomarker suited to identify patients that could benefit from YAP1/TAZ-TEAD directed therapeutic approaches within future clinical trials.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsBone NeoplasmsCell Line, TumorCell NucleusChick EmbryoHippo Signaling PathwayHumansProtein Serine-Threonine KinasesSarcomaSoft Tissue NeoplasmsTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsXenograft Model Antitumor AssaysYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingProtein Serine-Threonine KinasesTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsWWTR1 protein, humanYAP1 protein, humanYAP-Signaling Proteins

Identifiers

PMID31873172
PMCPMC6928161
OpenAlexW2995497868

What OpenQuestion holds

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Registered trials

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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.