SS18-SSX-Dependent YAP/TAZ Signaling in Synovial Sarcoma.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Ilka IsfortWolfgang Hartmann

Abstract

Synovial sarcoma is a soft tissue malignancy characterized by a reciprocal t(X;18) translocation. The chimeric SS18-SSX fusion protein acts as a transcriptional dysregulator representing the major driver of the disease; however, the signaling pathways activated by SS18-SSX remain to be elucidated to define innovative therapeutic strategies. Immunohistochemical evaluation of the Hippo signaling pathway effectors YAP/TAZ was performed in a large cohort of synovial sarcoma tissue specimens. SS18-SSX dependency and biological function of the YAP/TAZ Hippo signaling cascade were analyzed in five synovial sarcoma cell lines and a mesenchymal stem cell model in vitro. YAP/TAZ-TEAD-mediated transcriptional activity was modulated by RNAi-mediated knockdown and the small-molecule inhibitor verteporfin. The effects of verteporfin were finally tested in vivo in synovial sarcoma cell line-based avian chorioallantoic membrane and murine xenograft models as well as a patient-derived xenograft. A significant subset of synovial sarcoma showed nuclear positivity for YAP/TAZ and their transcriptional targets FOXM1 and PLK1. In synovial sarcoma cells, RNAi-mediated knockdown of SS18-SSX led to significant reduction of YAP/TAZ-TEAD transcriptional ...Continue Reading

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Citations

Dec 28, 2019·Journal of Experimental & Clinical Cancer Research : CR·Cinzia ZucchiniKatia Scotlandi
Dec 25, 2019·Scientific Reports·Ilka IsfortMarcel Trautmann
Oct 8, 2020·Current Oncology Reports·Marc El BeainoPatrick P Lin
Nov 13, 2020·Frontiers in Pharmacology·Changran Wei, Xiangqi Li
Jul 16, 2019·Biochimica Et Biophysica Acta. General Subjects·Fangjie YanBo Yang
Apr 9, 2021·JCI Insight·Iwao ShimomuraYusuke Yamamoto
Apr 14, 2021·Pathology, Research and Practice·Xiao FengYan Qi
Jul 24, 2021·Journal of Hematology & Oncology·Richard MiallotPhilippe Naquet
Aug 10, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Fan TangXia-Wei Wei

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