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Prevalence of the H...
Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
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Isfort, I. (author)
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Elges, S. (author)
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Cyra, M. (author)
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Berthold, R. (author)
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Renner, M. (author)
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Mechtersheimer, G. (author)
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- Åman, Pierre, 1953 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin,Institute of Biomedicine
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- Larsson, O. (author)
- Karolinska Institutet
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Ratner, N. (author)
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Hafner, S. (author)
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Simmet, T. (author)
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Schliemann, C. (author)
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Rossig, C. (author)
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Dirksen, U. (author)
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Grunewald, I. (author)
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Wardelmann, E. (author)
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Huss, S. (author)
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Hartmann, W. (author)
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Trautmann, M. (author)
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(creator_code:org_t)
- 2019-12-23
- 2019
- English.
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Abstract
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- 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 ofYAP1/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 ofYAP1 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 ofYAP1 and TAZ, corresponding to their transcriptionally active pool. Suppression ofYAP1/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 ofYAP1/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 fromYAP1/TAZ-TEAD directed therapeutic approaches within future clinical trials.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- growth in-vitro
- therapeutic target
- pathway
- yap
- fusion
- tead
- inhibition
- subset
- cells
- Science & Technology - Other Topics
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Isfort, I.
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Elges, S.
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Cyra, M.
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Berthold, R.
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Renner, M.
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Mechtersheimer, ...
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show more...
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Åman, Pierre, 19 ...
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Larsson, O.
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Ratner, N.
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Hafner, S.
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Simmet, T.
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Schliemann, C.
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Rossig, C.
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Dirksen, U.
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Grunewald, I.
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Wardelmann, E.
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Huss, S.
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Hartmann, W.
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Trautmann, M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Scientific Repor ...
- By the university
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University of Gothenburg
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Karolinska Institutet