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

长期以来滑膜肉瘤的病因不明，1994年Clark等人鉴定出t(X;18)嵌合基因，并将其命名为SYT-SSX。然后，SYT-SSX 的分子分析得到了进展，我们已经表明 SYT-SSX 对细胞具有致癌潜力（Nagai, M., et al., PNAS, 2001）。在这个项目中，发现 SYT-SSX 不仅与染色质重塑因子之一 hBRM 结合，而且与 BRG 结合（Gene Cells, 9, 2004），并且还显示出通过诱导p21（癌基因，24，2005）。此外，IGF2已被证明对滑膜肉瘤细胞的生长发挥重要作用(Oncogene, 25, 2006)。我们已经证明信号接头蛋白Crk对于滑膜肉瘤细胞系的致瘤性是不可或缺的(Mol.Cancer Res., 7, 2006)。该项目的目的之一是获得滑膜肉瘤治疗的可能靶分子。由于Crk敲低的细胞不会死亡，但恶性特征被消除，因此，Crk可能是治疗该肉瘤的治疗靶点，我们将继续分析Crk对滑膜肉瘤恶性特征的作用机制。

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.