DCD-Nck在大肠癌侵袭转移中的作用及蛇葡萄素的抑制机制研究

我们前期发现DCD酪氨酸磷酸化后能为Nck提供停泊点并与之结合,形成DCD-Nck-WASP-Arp2/3通路,对细胞骨架重排进行调控，同时激活Rac1，cdc42，调控肿瘤细胞运动。目前我们初步发现：DCD在大肠癌组织中表达，特别是大肠癌肝转移组；大肠癌组织及细胞中DCD-Nck存在相互作用；DCD-Nck共定位于大肠癌细胞，Nck在细胞连接处，DCD与之连接后共同发挥作用；蛇葡萄素能够抑制大肠癌细胞的迁移，减弱DCD-Nck相互作用。本研究拟进一步研究DCD-Nck在大肠癌的表达;比较正常对照组，蛇葡萄素组，5-氟尿嘧啶组DCD稳定转染的大肠癌LoVo细胞粘附侵袭迁移及细胞伪足改变；蛇葡萄素对DCD-NCK相互作用及共定位的破坏及机制，对DCD信号通路的的影响，对移植性人大肠癌肝转移裸鼠的的影响。通过体内外实验明确DCD与大肠癌及其转移的关系，揭示蛇葡萄素抗癌及减缓大肠癌侵袭机制

Our previous study found tyrosine phosphorylation protein--- DCD can combined with Nck and formed DCD-Nck-WASP-Arp2/3 pathway, effect regulation of the cytoskeleton, migration ,activated Rac1, Cdc42 ,and so on. .At present, we detect that the expression of DCD in colorectal cancer tissures (CRC), especially CRC patients with liver metastasis;DCD-Nck express in CRC tissues and LoVo cell; DCD and Nck co- localized in LoVo cell, Nck stay at cell junctions, DCD connected together with Nck and play role. Ampelopsin(AMP) can inhibit Lovo migrate , destroy DCD - Nck interaction. At further study, we will further confirm DCD and DCD - Nck in CRC patients tissures and serum employ pull down, ELISA and western blot ; Compare adhesion ,migration and cellular pseudopod of LoVo cell culture with control serum , AMP, 5 - fluorouracil (5 - FU),respectively； mechanism about AMP destroy DCD - NCK interaction. To further clarify DCD-Nck effect the invasion and metastasis of colorectal carcinoma and mechanism 0f inhibition of ampelopsin by DCD signal pathway.