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Figure S6 from Interdependence of SS18-SSX–driven YAP1 and β-Catenin Activation in Synovial Sarcoma

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posted on 2023-06-01, 08:21 authored by Ilka Isfort, Ruth Berthold, Lorena Heinst, Eva Wardelmann, Olle Larsson, Marcel Trautmann, Wolfgang Hartmann

Figure S6 shows that the mutual activation of YAP1/TAZ and β-catenin in SySa cells is impeded by knockdown of BAF complex subunits.

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Deutsche Forschungsgemeinschaft (DFG)

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ARTICLE ABSTRACT

Synovial sarcoma, a rare malignant soft tissue tumor, is characterized by a specific chromosomal translocation t(X;18). The resulting chimeric SS18-SSX fusion protein drives synovial sarcoma pathogenesis by integrating into the BAF complex and dysregulating gene transcription. Because previous functional analyses revealed a connection between SS18-SSX and the activity of the transcriptional coregulators YAP1/TAZ and β-catenin, respectively, this study examined a potential interdependence between these essential effector proteins in synovial sarcoma. In a large cohort of synovial sarcoma tissue specimens, IHC analyses revealed a substantial subset of synovial sarcoma with concurrent nuclear accumulation of YAP1/TAZ and β-catenin. In vitro, small-molecule inhibitor treatment, RNAi-mediated knockdown, and vector-based overexpression assays demonstrated that YAP1, TAZ, and β-catenin transcriptional activity is not only stimulated by the SS18-SSX fusion protein, but that they also mutually enhance each other's activation. These analyses showed the highest cooperative effect with overexpression of YAP1 in combination with β-catenin. Coimmunoprecipitation experiments detected nuclear interactions between YAP1, β-catenin, and the SS18-SSX fusion protein, the latter being an integral part of the BAF complex. Disruption of BAF complex assembly affected the coregulation of YAP1 and β-catenin, indicating that this chromatin remodeling complex plays a crucial role for interdependent YAP1 and β-catenin activation in synovial sarcoma cells. This study provides deeper insights into synovial sarcoma tumor biology demonstrating a mutual dependence between YAP1/TAZ and β-catenin transcriptional activity and a complex interplay with the SS18-SSX fusion protein within the BAF complex.

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