FMNL3基因在结直肠癌转移中的作用及其信号转导通路

项目名称： FMNL3基因在结直肠癌转移中的作用及其信号转导通路

项目编号： No.81201972

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2

项目作者： 曾元凤

作者单位： 江西省人民医院

项目金额： 23万元

中文摘要： FMNL3是新近发现的一种DRFs家族蛋白，有报道其与前列腺癌转移相关，但其调控转移的机制及是否与结直肠癌转移相关并不清楚。前期研究我们发现FMNL3的表达与结直肠癌转移潜能呈正相关；外源表达FMNL3能促进结直肠癌细胞侵袭转移，并使MMP-2 和MMP-9的表达上调。为探讨FMNL3调控结直肠癌转移的机制，本研究拟采用RT-QPCR、免疫组化、Western Blot技术检测结直肠癌组织和细胞中FMNL3的表达情况；然后观察该基因转染和干扰对结直肠癌细胞体内外生物学特性和RhoC/Pyk2/FAK信号通路的影响；并用免疫共沉淀和共定位技术分析FMNL3与RhoC、Pyk2、FAK的相互作用关系；最后分析PD98059、Ly294002及TAE226等抑制剂处理对该通路的影响。旨在阐明FMNL3参与结直肠癌转移调节的细胞信号途径，为结直肠癌转移预测、诊治和预后提供新基因靶点并奠定理论基础。

中文关键词： 结直肠癌；转移；FMNL3基因；信号通路；

英文摘要： FMNL3 is a new found member of DRFs. It was reported that FMNL3 is associated with metastasis in prostatic carcinoma, but so far, it is unknown what's the molecular mechanism of FMNL3 in regulating metastasis and whether FMNL3 correlates with metastasis in colorectal carcinoma (CRC).In our previous study, we found the positive correlation between FMNL3 expression and metastatic potential of CRC, and found when CRC cell lines were exogenously overexpressed FMNL3 gene,not only their capablility of invasion was enhanced, but also the expressions of MMP-2 and MMP-9 were increased. To clarify the molecular mechanism of FMNL3 regulation in CRC metastasis, firstly, we will investigate the expression of FMNL3 in CRC tissues and cell lines by RT-QPCR, immunohistochemistry and western blot. Then we will observe the effects of FMNL3 transfection and RNAi on CRC invasion and metastasis, so do the effects on the protein expression of RhoC/Pyk2/FAK signaling pathway. And then we will analysis the interaction relationship between FMNL3 and RhoC, Pyk2, FAK respectively by Co-immunoprecipitate and immuno-colocalization assays. Lastly, we will determine what component part is FMNL3 in the RhoC/Pyk2/FAK pathway by analysis the effects of the inhibitor PD98059, Ly294002 or TAE22 on the pathway. Our study aims to illustrate the m

英文关键词： colorectal carcinoma；metastasis；FMNL3 gene；signaling pathway；