转移相关基因FMNL2参与大肠癌Rho细胞运动信号通路的机制探讨

项目名称： 转移相关基因FMNL2参与大肠癌Rho细胞运动信号通路的机制探讨

项目编号： No.30870945

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 梁莉

作者单位： 南方医科大学

项目金额： 33万元

中文摘要： 本研究探讨了转移相关基因FMNL2参与大肠癌Rho细胞运动信号通路的新机制。首先观察了FMNL2-CT及FMNL2-NT对大肠癌细胞体内外生物学活性的影响；然后观察了FMNL2干扰或转染并结合抑制剂处理对Rho/ROCK通路、肌动蛋白聚合及MAL/SRF转录活性的影响，以及FMNL2干扰对LPA诱导的细胞体外侵袭能力、Rho/ROCK通路、肌动蛋白聚合及SRF转录活性的影响；最后检测了FMNL2与LARG、P115RhoGEF及RhoA的相互作用，观察LARG干扰对Rho/ROCK信号通路及细胞侵袭能力的影响。结果显示FMNL2-CT促进大肠癌细胞的增殖、运动、侵袭和转移能力，而FMNL2-NT抑制大肠癌细胞的体外侵袭能力；FMNL2通过与LARG的相互作用，与RhoA之间形成一个正反馈通路，从而增强Rho/ROCK通路活化、SRF转录活性及肌动蛋白的聚合能力，促进癌细胞的侵袭能力。这一新机制的提出将为阐述肿瘤转移机制提供新的线索，并为大肠癌转移预测、诊断及预后判断提供一个有效的靶点。

中文关键词： FMNL2；Rho细胞运动信号通路；转移；大肠癌

英文摘要： Our study explored the association of metastasis associated gene FMNL2 and Rho cell motility signaling pathway of colorectal carcinoma. First, we observed the effects of FMNL2-CT and FMNL2-NT on cell behaviors of colorectal carcinoma; Second, we observed the effect of FMNL2 silence or FMNL2 overexpression combined with three inhibitors on Rho/ROCK pathway, F-actin assembly and MAL/SRF transcription.Then the effect of FMNL2 silence on LPA-induced cell invasion in vitro, Rho/ROCK pathway, MAL/SRF transcription and F-actin assembly was also examined. Finally, we detected the interaction of FMNL2 with LARG, P115RhoGEF or RhoA and then observed the effect of LARG silence on cell invasion or Rho/ROCK pathway. Our results showed that FMNL2-CT promotes cell proliferation, motility, invasion and metastasis, while FMNL2-NT inhibites cell invasion of colorectal carcinoma. FMNL2 and RhoA constitute a positive feedback by interacting with LARG, which enhances the activations of Rho/ROCK pathway, SRF transcription and F-actin assembly and further promotes cancer cell invasion. The novel mechanism of FMNL2 involved in the Rho cell motility signaling pathway will provide new clue for illstruting metastasis mechanism and a novel target for metastasis forecast, diagnosis and prognosis evaluation of colorectal carcinoma.

英文关键词： FMNL2; Rho cell motility signaling pathway; Metastasis; Colorectal carcinoma