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Prevalence of the H...
Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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2019-12-23
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Springer Science and Business Media LLC,2019
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/290261
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https://gup.ub.gu.se/publication/290261URI
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https://doi.org/10.1038/s41598-019-56247-8DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:142831816URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
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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,1953Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xamapi
(author)
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Larsson, O.Karolinska Institutet
(author)
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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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Göteborgs universitetSahlgrenska Cancer Center
(creator_code:org_t)
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In:Scientific Reports: Springer Science and Business Media LLC92045-2322
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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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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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- 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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University of Gothenburg
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Karolinska Institutet