Synovial sarcoma – an aggressive soft-tissue cancer most commonly diagnosed in children and young adults – has a low survival rate and no effective systemic treatments. The oncogene SYT-SSX has been associated with synovial sarcoma, but how it drives tumorigenesis is unclear.
Josiane Eid, M.D., adjunct assistant professor of Cancer Biology, and colleagues investigated a possible link between SYT-SSX and Wnt/beta-catenin signaling – a developmental signaling pathway that is deregulated in many cancers.
Using synovial sarcoma cell cultures, sarcoma tumor xenografts and an SYT-SSX2 transgenic mouse model in which tumors develop that are similar to human synovial sarcoma tumors, they demonstrated that SYT-SSX2 activates Wnt/beta-catenin signaling. They showed that this signaling is necessary for synovial sarcoma growth and that inhibitors of Wnt signaling arrest synovial sarcoma tumor growth.
The findings, reported in the November issue of Cancer Discovery, reveal the critical role of Wnt/beta-catenin signaling in synovial sarcoma pathogenesis, and suggest that inhibitors of this pathway may be effective therapeutic agents for difficult-to-treat sarcomas.
This research was supported by the Alex’s Lemonade Stand Foundation, the National Institutes of Health (GM081635, GM103926, CA095103, CA113734) and the Department of Veterans Affairs.
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