SNCG调控细胞骨架重组促进上皮性卵巢癌侵袭转移的分子机制研究

Ovarian cancer is a common gynaecological malignancy associated with poor outcome, and 70% of the disease is epithelial ovarian cancer (EOC). Searching for new specific antibody biomarkers and investigating their mechanisms play an essential role in the eraly diagnosis and treatment of EOC. Our previous study showed that Synuclein was identifid in the EOC plasma samples compared with controls using an innovative ‘reverse capture antibody microarray’ platform. By immunohistochemistry and Western blot, γ-Synuclein (SNCG) overexpression is associated with an unfavorable prognosis and is an independent prognostic factor for EOC, which suggests that SNCG may be a novel and crucial predictor for EOC metastasis. Based on comprehensive literatures and our previous study, we supposed that SNCG-Rho GTPases-WASP signaling pathway played a key role in regulation of actin cytoskeleton and leading to cell migration of EOC. In the present study, we aim to investigate the mechanisms in metastasis of EOC that are caused by SNCG overexpression. There are three goals in our study: 1. Characterization of the cell biology and molecular biology changes after knockdown and upregulated SNCG of EOC cells. 2. Characterization of the effect of SNCG-Rho-WASP signaling interaction cytoskeleton organization. 3. Characterization of the role of SNCG in metastatic dissemination in vivo. We wish to investigate the molecular mechanism of SNCG regulation of actin cytoskeleton in promoting invasion and metastasis of EOC. This study will provide a new idea in the eraly diagnosis and treatment of EOC.

卵巢癌是常见的妇科恶性肿瘤，其中70%为上皮性卵巢癌（EOC），探寻新的肿瘤标志物并深入研究其作用机制对EOC早期诊断及治疗具有重要意义。课题组前期研究采用反向捕获抗体芯片技术在EOC早期诊断研究中发现差异性蛋白Synuclein，通过验证提示其家族成员γ-Synuclein（SNCG）可能与EOC的侵袭转移相关。综合文献及前期研究，我们推测SNCG-Rho GTPases-WASP信号途径在SNCG调控EOC细胞骨架重组进而促进癌细胞迁移中扮演重要角色。因此，本项目拟通过探讨SNCG对卵巢癌细胞恶性生物学特征的影响；探析SNCG-Rho GTPases-WASP信号转导途径激活癌细胞迁移机制；以及体内研究评估抑制SNCG对卵巢癌的治疗效果三方面，阐明SNCG促进EOC细胞侵袭转移的分子机制这一科学问题。本课题以期为EOC早期诊断及靶点治疗提供新的思路。