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The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma

ABSTRACT: Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β -catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β -catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation. SS18SSX expressing C3H cells vs control: no replicates. WNT-stimulated C3H cells vs controls: 3 replicates per condition

ORGANISM(S): Mus musculus  

SUBMITTER: Carlo Fusco  Giulia Fregni   Michel Aguet   Victor Fernandes Vieira   Tanja Petricevic   Ivan Stamenkovic   Luisa Cironi   Paolo Provero   Igor Letovanec   Sandrine Cornaz    

PROVIDER: E-GEOD-78159 | ArrayExpress | 2016-02-27



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