Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Isfort, Ilka, Elges, Sandra, Cyra, Magdalene, Berthold, Ruth, Renner, Marcus, Mechtersheimer, Gunhild, Åman, Pierre, Larsson, Olle, Ratner, Nancy, Hafner, Susanne, Simmet, Thomas, Schliemann, Christoph, Rossig, Claudia, Dirksen, Uta, Grünewald, Inga, Wardelmann, Eva, Huss, Sebastian, Hartmann, Wolfgang, Trautmann, Marcel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928161/
https://www.ncbi.nlm.nih.gov/pubmed/31873172
http://dx.doi.org/10.1038/s41598-019-56247-8
_version_ 1783482424153341952
author Isfort, Ilka
Elges, Sandra
Cyra, Magdalene
Berthold, Ruth
Renner, Marcus
Mechtersheimer, Gunhild
Åman, Pierre
Larsson, Olle
Ratner, Nancy
Hafner, Susanne
Simmet, Thomas
Schliemann, Christoph
Rossig, Claudia
Dirksen, Uta
Grünewald, Inga
Wardelmann, Eva
Huss, Sebastian
Hartmann, Wolfgang
Trautmann, Marcel
author_facet Isfort, Ilka
Elges, Sandra
Cyra, Magdalene
Berthold, Ruth
Renner, Marcus
Mechtersheimer, Gunhild
Åman, Pierre
Larsson, Olle
Ratner, Nancy
Hafner, Susanne
Simmet, Thomas
Schliemann, Christoph
Rossig, Claudia
Dirksen, Uta
Grünewald, Inga
Wardelmann, Eva
Huss, Sebastian
Hartmann, Wolfgang
Trautmann, Marcel
author_sort Isfort, Ilka
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6928161
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-69281612019-12-27 Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone Isfort, Ilka Elges, Sandra Cyra, Magdalene Berthold, Ruth Renner, Marcus Mechtersheimer, Gunhild Åman, Pierre Larsson, Olle Ratner, Nancy Hafner, Susanne Simmet, Thomas Schliemann, Christoph Rossig, Claudia Dirksen, Uta Grünewald, Inga Wardelmann, Eva Huss, Sebastian Hartmann, Wolfgang Trautmann, Marcel Sci Rep Article 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. Nature Publishing Group UK 2019-12-23 /pmc/articles/PMC6928161/ /pubmed/31873172 http://dx.doi.org/10.1038/s41598-019-56247-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Isfort, Ilka
Elges, Sandra
Cyra, Magdalene
Berthold, Ruth
Renner, Marcus
Mechtersheimer, Gunhild
Åman, Pierre
Larsson, Olle
Ratner, Nancy
Hafner, Susanne
Simmet, Thomas
Schliemann, Christoph
Rossig, Claudia
Dirksen, Uta
Grünewald, Inga
Wardelmann, Eva
Huss, Sebastian
Hartmann, Wolfgang
Trautmann, Marcel
Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
title Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
title_full Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
title_fullStr Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
title_full_unstemmed Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
title_short Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
title_sort prevalence of the hippo effectors yap1/taz in tumors of soft tissue and bone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928161/
https://www.ncbi.nlm.nih.gov/pubmed/31873172
http://dx.doi.org/10.1038/s41598-019-56247-8
work_keys_str_mv AT isfortilka prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT elgessandra prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT cyramagdalene prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT bertholdruth prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT rennermarcus prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT mechtersheimergunhild prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT amanpierre prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT larssonolle prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT ratnernancy prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT hafnersusanne prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT simmetthomas prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT schliemannchristoph prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT rossigclaudia prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT dirksenuta prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT grunewaldinga prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT wardelmanneva prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT husssebastian prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT hartmannwolfgang prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone
AT trautmannmarcel prevalenceofthehippoeffectorsyap1tazintumorsofsofttissueandbone