肝转移是许多消化道肿瘤的关键致死因素。肿瘤肝转移是一个复杂的多步骤过程，而肿瘤细胞于肝脏的定植是肝转移的限速步骤，但该限速步骤中起关键作用的分子尚不清楚。为模拟体内肿瘤的肝定植过程，我们构建了脾脏注射-肝定植模型，利用该模型我们筛选获得了一系列高肝定植能力的肿瘤细胞株。利用表达谱芯片筛选其中差异表达基因，联合临床资料分析、功能学验证，初步锚定GJA1-在高肝定植细胞株中高表达，指示着肿瘤更差的预后；GJA1高表达显著促进肿瘤细胞的肝定植，促进体内血管生成和体外小管形成；GJA1促进肿瘤细胞与血管内皮细胞的粘附。因此本课题拟进一步探究GJA1介导的肿瘤细胞与肝血窦内皮细胞的粘附、物质传递，其调控的下游分子级联反应，最终揭示其在肿瘤肝定植过程中的作用及机制。为全面认识肿瘤肝转移过程中肿瘤细胞与组织微环境的相互作用及介导该作用的关键分子事件提供新的视角，为肿瘤肝转移提供早期预警标志物及治疗靶点。

Liver metastasis is the primary lethal factor of many digestive system cancers. Liver metastasis is a complex multiple-procedures process. The colonization of cancer cells to liver is the limiting step of liver metastasis. However, which molecules play critical roles in this step is still unknown. To mimic the liver colonization of cancer cells in vivo, we constructed spleen injection-liver colonization mouse model. Using this model, we selected and acquired a series of cancer cells with increased liver colonization potential. Using gene expression microarray, the analysis of clinical data, and functional experiments, we focus on GJA1, which is highly expressed in cancer cells with increased liver colonization potential and associated with poor prognosis of several cancers. GJA1 promotes liver colonization of cancer cells, in vivo angiogenesis, and in vitro tube formation. GJA1 promotes the adhesion between cancer cells and vascular endothelial cells. In this study, we will further study the intercellular adhesion and molecules transfer between cancer cells and liver sinusoidal endothelial cells mediated by GJA1, the downstream molecular events caused by GJA1, and lastly the roles and mechanisms of GJA1 in liver colonization of cancer cells. This study will provide a novel visual angle to understand the interaction between cancer cells and microenvironment in the process of liver colonization, and furthermore the critical molecules mediating the interaction. This study will provide early diagnostic biomarker and therapeutic target for liver metastasis.