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Sci Rep. 2019 Dec 23;9(1):19704. doi: 10.1038/s41598-019-56247-8.

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

Author information

1
Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.
2
Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.
3
Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
4
Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
5
Departments of Oncology & Pathology, The Karolinska Institute, Stockholm, Sweden.
6
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America.
7
Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, Ulm, Germany.
8
Department of Medicine A, Hematology and Oncology, Münster University Hospital, Münster, Germany.
9
Department of Pediatric Hematology and Oncology, University Children´s Hospital Münster, Münster, Germany.
10
Cells in Motion Cluster of Excellence (EXC 1003 - CiM), University of Münster, Münster, Germany.
11
Pediatrics III, West German Cancer Center, University Hospital Essen, Essen, Germany.
12
German Cancer Consortium (DKTK), Essen, Germany.
13
Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany. wolfgang.hartmann@ukmuenster.de.
14
Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany. wolfgang.hartmann@ukmuenster.de.
15
Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany. marcel.trautmann@ukmuenster.de.
16
Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany. marcel.trautmann@ukmuenster.de.

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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