title: 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.
authors.affiliation: Institute of Pathology University of Lausanne and CHUV Lausanne, Switzerland.
authors.forename: Luisa
authors.initials: L
authors.lastname: Cironi
authors.affiliation: Institute of Pathology University of Lausanne and CHUV Lausanne, Switzerland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Petricevic
authors.affiliation: Institute of Pathology University of Lausanne and CHUV Lausanne, Switzerland.
authors.forename: Victor
authors.initials: V
authors.lastname: Fernandes Vieira
authors.affiliation: Center for Translational Genomics and Bioinformatics San Raffaele Scientific Institute Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
authors.affiliation: Institute of Pathology University of Lausanne and CHUV Lausanne, Switzerland.
authors.forename: Carlo
authors.initials: C
authors.lastname: Fusco
authors.affiliation: Institute of Pathology University of Lausanne and CHUV Lausanne, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cornaz
authors.affiliation: Institute of Pathology University of Lausanne and CHUV Lausanne, Switzerland.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fregni
authors.affiliation: Institute of Pathology University of Lausanne and CHUV Lausanne, Switzerland.
authors.forename: Igor
authors.initials: I
authors.lastname: Letovanec
authors.affiliation: Swiss Institute for Experimental Cancer Research Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Aguet
authors.affiliation: Institute of Pathology University of Lausanne and CHUV Lausanne, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Stamenkovic
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins; D020869:Gene Expression Profiling / Q000379:methods*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D056970:Co-Repressor Proteins; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins; C587877:SS18-SSX1 fusion protein; D051820:TCF Transcription Factors; C499043:TLE1 protein, human; D014157:Transcription Factors; D051176:beta Catenin; D006655:Histone Deacetylases