American Association for Cancer Research
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Supplementary Figure S9 from Targeting the Wnt Pathway in Synovial Sarcoma Models

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journal contribution
posted on 2023-04-03, 20:26 authored by Whitney Barham, Andrea L. Frump, Taylor P. Sherrill, Christina B. Garcia, Kenyi Saito-Diaz, Michael N. VanSaun, Barbara Fingleton, Linda Gleaves, Darren Orton, Mario R. Capecchi, Timothy S. Blackwell, Ethan Lee, Fiona Yull, Josiane E. Eid

Supplementary Figure S9 - PDF file 867K,Figure S9: The SYT-SSX2 domain SSXRD executes �-catenin activation and myogenic differentiation



Synovial sarcoma is an aggressive soft-tissue malignancy of children and young adults, with no effective systemic therapies. Its specific oncogene, SYT–SSX (SS18–SSX), drives sarcoma initiation and development. The exact mechanism of SYT–SSX oncogenic function remains unknown. In an SYT–SSX2 transgenic model, we show that a constitutive Wnt/β-catenin signal is aberrantly activated by SYT–SSX2, and inhibition of Wnt signaling through the genetic loss of β-catenin blocks synovial sarcoma tumor formation. In a combination of cell-based and synovial sarcoma tumor xenograft models, we show that inhibition of the Wnt cascade through coreceptor blockade and the use of small-molecule CK1α activators arrests synovial sarcoma tumor growth. We find that upregulation of the Wnt/β-catenin cascade by SYT-SSX2 correlates with its nuclear reprogramming function. These studies reveal the central role of Wnt/β-catenin signaling in SYT–SSX2-induced sarcoma genesis, and open new venues for the development of effective synovial sarcoma curative agents.Significance: Synovial sarcoma is an aggressive soft-tissue cancer that afflicts children and young adults, and for which there is no effective treatment. The current studies provide critical insight into our understanding of the pathogenesis of SYT–SSX-dependent synovial sarcoma and pave the way for the development of effective therapeutic agents for the treatment of the disease in humans. Cancer Discov; 3(11); 1286–1301. ©2013 AACR.This article is highlighted in the In This Issue feature, p. 1207