转移是胃癌患者死亡的首要原因。G蛋白通路抑制子2（GPS2）是近年新发现肿瘤相关蛋白，在胃癌中的作用尚不清楚。前期研究发现，GPS2在胃癌组织和细胞系中低表达，且其表达与转移和预后不良负相关；细胞实验发现GPS2和蛋白激酶TOPK存在结合，并且该结合使得TOPK与转移相关信号蛋白ERK2结合降低；过表达和敲减GPS2，ERK2活化和细胞侵袭迁移力均发现变化。推测GPS2可能竞争性抑制TOPK和ERK2结合进而抑制胃癌转移。本课题拟通过：临床样本回顾性研究GPS2与胃癌病理、转移、预后及ERK2活化的相关性；细胞水平研究GPS2与TOPK结合区域及调控ERK2活性而抑制胃癌转移的作用；动物模型验证GPS2在体内抑制胃癌转移的作用，阐明GPS2竞争性结合TOPK抑制ERK2活化进而抑制胃癌转移的机制。本研究将为胃癌的分子诊断和基因治疗提供新的思路。

Metastasis is the leading cause of death in gastric cancer patients. The G-protein pathway suppressor 2 (GPS2) was found to be correlated with tumor in recent years, but its role in gastric cancer is not yet clear. In our previous study, we found that GPS2 has low expression in gastric cancer tissues and gastric cancer cell lines, and its expression negatively correlates with metastasis and poor prognosis. GPS2 has interaction with protein kinase TOPK, which reduces the interaction of TOPK and ERK2, a metastasis related protein. Overexpression and knockdown GPS2 affect both ERK2 activation level and cell invasion and migration abilities. In the current project, we focus on the mechanism of GPS2 in inhibiting gastric cancer metastasis through competitively suppressing the interaction of TOPK and ERK2. This study includes three aspects to clarify the molecular mechanism of GPS2 in inhibiting gastric cancer metastasis through competitively combination of TOPK and inhibition of ERK2 activation: We study the correlation between the GPS2 expression, ERK2 activation and the pathology, metastasis and prognosis of gastric cancer specimens; We try to find out the binding region and site of GPS2 and TOPK, regulation of ERK2 activation and inhibition of gastric cancer metastasis by cell models. We verify if GPS2 can suppress tumor growth and metastasis by in vivo nude mouse model. Our study will show that GPS2 may be an important marker for human gastric cancer metastasis and prognosis and provide potential therapeutic target.