Flotillin-2在鼻咽癌中的活化、作用和分子机制研究

Nasopharyngeal carcinoma (NPC) is an endemic cancer with high incidence in Southeast Asia and Southern China. NPC often metastasizes to lymphnodes nearby at very early stage. By using suppression subtractive hybridization (SSH) and other techniques, we identified Flotillin-2 (FLOT2)as a differentially expressed gene between 5-8F (highly tumorigenic and metastatic) and 6-10B (tumorigenic and non-metastatic) NPC cells, which exhibited much higher expression in 5-8F cells. Our preliminary gene transfection and RNA interference(RNAi) results showed that FLOT2 expression could increase the proliferation ability and motility of NPC cells. Our immunohistochemical results demonstrated that FLOT2 was highly expressed in NPC tissues with even higher expression level in metastatic NPC tissues, indicating that it may be related with carcinogenesis and progression of NPC. In this project, we will further investigate the expression and activation mechanism of FLOT2 in NPC, comprehensively explore its function in NPC by gene transfection and RNAi methods, and clarify the molecular mechanism underlying its participating in occurrence and progression of NPC using chip analysis, yeast two-hybrid system, signaling pathway detection, EMT assay, etc. Through the implementation of this project, we will identify the expression, activation, function and molecular mechanism of FLOT2 in NPC, providing important clues for developing a novel strategy for early diagnosis and treatment of NPC by use of FLOT2 as a molecular target.

鼻咽癌（NPC）在东南亚和我国南方高发，易发生早期转移。Flotillin-2(FLOT2)是我们用抑制性消减杂交等技术从NPC细胞系5-8F(高成瘤、高转移)和6-10B(成瘤、不转移)筛出的差异表达基因，在5-8F中高表达。初步的转基因和RNA干扰(RNAi)结果表明FLOT2促进NPC细胞的增殖和运动能力。免疫组化结果显示，FLOT2在NPC中高表达，在转移的NPC中表达更高，可能与NPC发生发展相关。本项目拟进一步研究FLOT2在NPC中的表达及活化机制，利用转基因和RNAi等手段全面研究FLOT2在NPC发生发展中的作用，结合芯片、酵母双杂交、信号通路检测、EMT分析等方法深入探讨其作用机理。通过本项目的实施，我们可以明确FLOT2在NPC中表达、活化、功能及作用分子机制，为发展以FLOT2为靶标的NPC早期诊治的新策略提供重要线索。

鼻咽癌（NPC）在东南亚和我国南方高发，易发生早期转移。Flotillin-2（FLOT2）是我们用抑制性消减杂交等技术从NPC细胞系5-8F（高成瘤、高转移）和6-10B（成瘤、不转移）筛出的差异表达基因，在5-8F中高表达。通过本项目的实施，明确了FLOT2与NPC发生、发展、转移的相关性；研究了FLOT2在NPC中活化的机制；明确了FLOT2在NPC中的功能和作用分子机制；确定了FLOT2和FLOT1之间存在相互作用；找到了NPC中FLOT2相互作用蛋白和相关蛋白并做了初步的功能研究；制备了具有杀伤肿瘤特性的纳米颗粒，为发展以FLOT2为靶标的NPC早期诊治新策略奠定了实验基础。