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Cited by 35Hippo pathway signaling and YAP/TAZSarcoma Diagnosis and TreatmentTGF-β signaling in diseases

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

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Isfort, Ilka, Elges, Sandra, Cyra, Magdalene, Berthold, Ruth, Renner, Marcus, Mechtersheimer, Gunhild, Åman, Pierre, Larsson, Olle +11 more·2019·Scientific Reports
DOI 10.1038/s41598-019-56247-8PMC PMC6928161
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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.

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  • In DDLS, UPS, and MFS, the Hippo pathway is frequently deregulated through increased expression of the transcriptional coactivators YAP and TAZ.

    “In DDLS, UPS, and MFS, the Hippo pathway is frequently deregulated through increased expression of the transcriptional coactivators YAP and TAZ (9, 23–25).”

    From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [25]

    The Results (page unavailable in our copy) report nuclear YAP1 positivity in 32% and TAZ positivity in 31% of DDLS specimens, supporting YAP1/TAZ activity in a subset of DDLS. The Methods list the ten tumor types studied but do not include UPS or MFS; the paper therefore does not establish frequent deregulation through increased YAP1/TAZ expression in those two types. (LLM, conf=0.87)

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Research works printed but not linked: 31

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Authors
Isfort, I., Elges, S., Cyra, M., Berthold, R., Renner, M., Mechtersheimer, G., Åman, P., Larsson, O., Ratner, N., Hafner, S., Simmet, T., Schliemann, C., Rossig, C., Dirksen, U., Grünewald, I., Wardelmann, E., Huss, S., Hartmann, W., & Trautmann, M.
Affiliations
  • University Hospital Münster (DE)
  • University Hospital Heidelberg (DE)
  • University of Gothenburg (SE)
  • Karolinska Institutet (SE)
  • Cincinnati Children's Hospital Medical Center (US)
  • Universität Ulm (DE)
  • Essen University Hospital (DE)
Corresponding author
  • Hartmann, Wolfgang
  • Trautmann, Marcel
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-12-23
Volume
9
Issue
1
Pages
19704-19704
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-56247-8
PMC
PMC6928161
OpenAlex
W2995497868
Cited by
35
References
34
Citations by year
2026: 6 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 7 · 2020: 1
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (HA 4441/2-1)
  • Deutsche Krebshilfe (#108128)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
YAP, TAZ, Hippo signaling pathway, soft tissue sarcoma, bone tumors, angiosarcoma, Ewing sarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, solitary fibrous tumor, synovial sarcoma, myxoid liposarcoma, TEAD transcription factors, nuclear protein expression, therapeutic target, biomarkers
MeSH terms
Hippo Signaling Pathway, YAP-Signaling Proteins, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Animals, Bone Neoplasms, Cell Nucleus, Chick Embryo, Humans, Sarcoma, Soft Tissue Neoplasms, Transcription Factors, Trans-Activators, Protein Serine-Threonine Kinases, Xenograft Model Antitumor Assays, Cell Line, Tumor, Adaptor Proteins, Signal Transducing

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