Synovial sarcoma is a soft tissue tumor of the joints that affects young adults. It is characterized by a chromosomal translocation t(X; 18;pl 1;ql 1) that juxtaposes the SYT gene on chromosome 18 and the SSX gene on the X chromosome, resulting in the fusion, SYT-SSX. In the cancer, SYT-SSX is thought to exert a dominant gain of function, while the wt SYT allele is significantly down regulated, leading to loss of SYT normal function. a-catenin is the mediator of the wnt pathway, an active program in development and cancer. We found that SYT associates with beta-catenin in the nucleus and appears to suppress its function, while SYT-SSX activates it. The objective of this proposal is to characterize the functional relationship between SYT and beta-catenin, and its deregulation by SYT-SSX, in adult tissue and development. In addition, we will identify the nuclear components involved in this process and their role in mediating SYT and SYT-SSX effects on a-catenin.
The aim of this research proposal is to help gain a clearer understanding of synovial sarcoma development.
| Barco, Roy; Garcia, Christina B; Eid, Josiane E (2009) The synovial sarcoma-associated SYT-SSX2 oncogene antagonizes the polycomb complex protein Bmi1. PLoS One 4:e5060 |
| Chittezhath, Manesh; Frump, Andrea L; Jourquin, Jerome et al. (2008) The proto-oncoprotein SYT (SS18) controls ATP release and regulates cyst formation by polarized MDCK cells. Exp Cell Res 314:3551-62 |
| Barco, Roy; Hunt, Laura B; Frump, Andrea L et al. (2007) The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskeleton through activation of the ephrin pathway. Mol Biol Cell 18:4003-12 |
| Pretto, D; Barco, R; Rivera, J et al. (2006) The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the nucleus and associates with it in an active complex. Oncogene 25:3661-9 |
