Analysis of human synovial sarcoma oncoprotein SYT-SSX and its therapeutic application.

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The cause of synovial sarcoma had been unknown for long time, and in 1994, Clark et al., identify the chimeric gene of t(X;18) and named it SYT-SSX. Then molecular analysis of SYT-SSX has been advanced and we have shown that SYT-SSX serves oncogenic potential on cells (Nagai, M., et al., PNAS, 2001).In this project, SYT-SSX was found to bind to not only one of the chromatin remodeling factors, hBRM, but to BRG (Gene Cells, 9, 2004), and also shown to induce cellular senescence by the induction of p21 (Oncogene, 24, 2005). Furthermore, IGF2 has been shown to play an important role for growth of synovial sarcoma cells (Oncogene, 25, 2006). We have shown that signaling adaptor protein Crk is indispensable for tumorigenesity of synovial sarcoma cell lines (Mol. Cancer Res., 7, 2006).One of the purpose of this project is to obtain the possible target molecules for synovial sarcoma treatment. As Crk knockdown cells is not going to die, but the malignant features were eliminated, thus, Crk may be the therapeutic target for the treatment of this sarcoma, and we will continue to analyze the mechanism of Crk for malignant character of synovial sarcoma.