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Updated: Jan 28, 2026
13:05
De Novo Generation of Somatic Stem Cells by YAP/TAZ
Published on: May 7, 2018
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SS18-SSX-Dependent YAP/TAZ Signaling in Synovial Sarcoma
Ilka Isfort1,2, Magdalene Cyra1,2, Sandra Elges2
1Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.
Summary
Synovial sarcoma is driven by SS18-SSX, which activates YAP/TAZ signaling. Targeting this pathway with verteporfin inhibits tumor growth, offering a new therapeutic strategy for this soft tissue malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Synovial sarcoma is a soft tissue malignancy driven by the SS18-SSX fusion protein.
- The precise signaling pathways regulated by SS18-SSX remain incompletely understood, hindering targeted therapy development.
Purpose of the Study:
- To investigate the role of the Hippo signaling pathway effectors YAP/TAZ in synovial sarcoma pathogenesis.
- To explore the therapeutic potential of targeting YAP/TAZ signaling in synovial sarcoma.
Main Methods:
- Immunohistochemical analysis of YAP/TAZ in synovial sarcoma tissues.
- In vitro studies using synovial sarcoma cell lines and mesenchymal stem cells to assess SS18-SSX dependency and YAP/TAZ function.
- RNAi-mediated knockdown and small-molecule inhibitor (verteporfin) treatment to modulate YAP/TAZ-TEAD activity.
- In vivo validation in avian chorioallantoic membrane and xenograft models.
Main Results:
- Nuclear YAP/TAZ and downstream targets (FOXM1, PLK1) were detected in a significant subset of synovial sarcomas.
- SS18-SSX knockdown reduced YAP/TAZ-TEAD activity, while SS18-SSX overexpression induced aberrant YAP/TAZ signaling via an IGF-II/IGF-IR loop.
- Verteporfin treatment and RNAi-mediated modulation of YAP/TAZ-TEAD significantly inhibited tumor cell growth in vitro and in vivo.
Conclusions:
- SS18-SSX drives YAP/TAZ signaling, playing a critical role in synovial sarcoma development.
- This study elucidates a key oncogenic signaling network in synovial sarcoma.
- Targeting SS18-SSX-driven YAP/TAZ pathways represents a promising therapeutic strategy for synovial sarcoma.
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