RRC ID 77024
Author Cironi L, Petricevic T, Fernandes Vieira V, Provero P, Fusco C, Cornaz S, Fregni G, Letovanec I, Aguet M, Stamenkovic I.
Title The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.
Journal Sci Rep
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.
Volume 6
Pages 22113
Published 2016-2-24
DOI 10.1038/srep22113
PII srep22113
PMID 26905812
PMC PMC4764983
MeSH Animals Axin Protein / genetics Axin Protein / metabolism Blotting, Western Cell Line Cell Line, Tumor Co-Repressor Proteins Gene Expression Profiling / methods* Histone Deacetylases / genetics Histone Deacetylases / metabolism Humans Mice Microscopy, Confocal Oncogene Proteins, Fusion / genetics* Oncogene Proteins, Fusion / metabolism RNA Interference Repressor Proteins / genetics Repressor Proteins / metabolism Reverse Transcriptase Polymerase Chain Reaction Sarcoma, Synovial / genetics Sarcoma, Synovial / metabolism Sarcoma, Synovial / pathology TCF Transcription Factors / genetics TCF Transcription Factors / metabolism Transcription Factors / genetics* Transcription Factors / metabolism Wnt Signaling Pathway / genetics* beta Catenin / genetics beta Catenin / metabolism
IF 3.998
Human and Animal Cells HS-SY-II(RCB2231)