结肠癌转移相关基因-1通过Twist1/VE-cadherin通路调控胃癌拟态血管形成的机制研究

拟态血管（VM）是肿瘤功能性微循环形式。我们的前期研究证实胃癌组织中存在VM，且与结肠癌转移相关基因-1（MACC1）表达正相关，但未见MACC1调控胃癌的VM形成的报道。我们的预实验结果显示MACC1可上调Twist1及VE-cadherin表达，现已知Twist1/VE-cadherin是调控VM的重要信号通路。因此，我们假设：①MACC1通过Twist1/VE-cadherin通路调控胃癌VM形成；②作为转录因子的MACC1，可在转录和/或mRNA剪接水平上调Twist1/VE-cadherin mRNA表达；③MACC1重要的下游信号通路HGF/c-Met可激活Twist1/VE-cadherin通路并参与胃癌VM的调控。本课题拟从临床、动物、细胞和分子四个水平，证实MACC1通过Twist1/VE-cadherin信号通路调控VM形成，为胃癌抗肿瘤血管生成治疗提供实验依据。

VM is a functional form of microcirculation of tumor. Our prophase research confirmed that VM, which was found existing in gastric carcinoma tissue, has a positive correlation with the expression of MACC1. However, it is unkown whether MACC1 regulates VM formation in gastric carcinoma.Our preliminary experimental results show that MACC1 upregulates the expression of Twist1 and VE-cadherin which are the important molecules regulating VM. Therefore, we put forward three hypotheses: ①MACC1 regulates VM formation in gastric carcinoma through Twist1/VE-cadherin pathway; ②MACC1 upregulates the expression of Twist1/ VE-cadherin mRNA in transcription and/or mRNA splicing level. ③HGF/c-Met could activate Twist1/VE-cadherin pathway and participate in the regulation of VM in gastric carcinoma as the important signaling pathways downstream of MACC1.This study will demonstrate that MACC1 regulates vasculogenic mimicry formation through Twist1/VE-cadherin pathway in clinical, animal, cellular and molecular levels, and provides an experimental basis for anti-tumor angiogenesis therapy in gastric carcinoma.