SYK(S)对肝癌侵袭转移的影响及其机制研究

项目名称： SYK(S)对肝癌侵袭转移的影响及其机制研究

项目编号： No.81201634

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 洪健

作者单位： 广州医科大学

项目金额： 23万元

中文摘要： 我们的前期研究发现：肝癌SYK基因两种异构体的生物学功能与临床预后价值相反，其中全长型SYK(L)具有抑癌基因功能，能够抑制肝癌细胞增殖和裸鼠体内成瘤等，是肝癌患者术后生存较好的预测指标；而缩短型SYK(S)具有潜在癌基因功能，其表达水平与肝癌恶性增殖及复发转移密切相关，但具体作用机制尚不明确。本项目拟采用构建病毒感染的稳定细胞株、基因转染、RNA干扰、Transwell小室、细胞免疫荧光等方法，探讨SYK(S)对肝癌侵袭转移的影响及其相关机制；其次建立SYK(S)过表达或敲低的裸鼠肝脏原位移植瘤模型，观察SYK(S)对肿瘤原位侵袭及远处肺转移的影响；最后检测至少120例肝癌标本中SYK(S)与其信号通路中的相关蛋白的表达，分析SYK(S)单独或联合其信号通路相关蛋白在肝癌术后复发转移中的预测价值。本研究结果将有助于阐明肝癌侵袭转移的机制，以及为肝癌靶向治疗提供新的理论依据。

中文关键词： 肝细胞癌；SYK(S)；侵袭；转移；

英文摘要： Our preliminary study indicated that two isoforms of SYK gene, the full length form SYK(L) and short form SYK(S), had opposite biologic functions and prognostic value in human hepatocellular carcinoma (HCC). SYK(L) acts as a tumor suppressor which could inhibited proliferation and xenograft growth, and the presence of SYK(L) expression was associated with better outcome among HCC patients after resection of primary tumor. While SYK(S) plays the opposite role as oncogene whose expression level was associated with malignant proliferation and recurrence of HCC. However, the role of SYK(S) in invasion and metastasis of HCC have been rarely reported in literature. In this project, multiple methods including stable cell lines constructed with retroviral packaging system, gene transfection, RNA interference, Transwell assay and immunofluorescence staining will be used to explore whether SYK(S) has effects on invasion and metastasis in HCC cells and its related molecular mechanism. Moreover, metastatic assay in a nude mice model with orthotopic HCCs, in which SYK(S) is retrovirally overexpressed or knocked-down, will be used to investigate the effects of SYK(S) on liver invasion and lung metastasis in vivo. In addition, with the detection of the expression of SYK(S) and related proteins involved in its signal pathway in

英文关键词： hepatocellular carcinoma；SYK(S)；invasion；metastasis；