胃癌是严重威胁我国人民健康的恶性肿瘤，远端转移是胃癌患者死亡的主要原因之一。然而目前对于胃癌远端转移缺少有效的临床策略，我们对其转移机制了解也较少。申请人长期围绕肿瘤转移机制开展相关研究，前期在Gastroenterology报道了Ephrin A1对胃癌转移至关重要。那么，Ephrin A1是如何调控胃癌远端转移？我们初步研究提示Ephrin A1能促进胃癌细胞EMT状态，提高胃癌细胞跨内皮侵袭和肿瘤干性，并受到miRNA200家族调控。基于前期研究的科学假设，本项目将聚焦胃癌细胞早期定植转移阶段，通过分子、细胞、动物、临床等层面，重点研究Ephrin A1调控胃癌细胞EMT可塑性的上下游通路，阐明Ephrin A1影响胃癌细胞跨内皮侵袭穿出血管并维持肿瘤干性从而促进胃癌转移的机制。本课题的完成将有助于深入了解胃癌远端转移的分子机理，为胃癌转移的诊断干预提供新的理论依据与潜在的分子靶点。

Gastric cancer seriously threatens the people’s health in China. Distant metastasis is one of the leading causes of death in patients with gastric cancer. However, there is currently no effective clinical strategy for distant metastasis of gastric cancer, and we have less understanding of gastric cancer metastasis. Applicants have long been conducting research on the mechanism of tumor metastasis. Our previous results published on Gastroenterology reported that Ephrin A1 is essential for gastric cancer metastasis. Regarding the mechanism for Ephrin A1 regulating gastric cancer cell metastasis? Our preliminary study suggests that Ephrin A1 can regulate EMT status in gastric cancer cells, promote trans-endothelial invasion and maintain stemness of gastric cancer cells. Ephrin A1 also can be targeted by miRNA200 family. Based on the previous research, we propose a scientific hypothesis. This project will focus on the early stage of colonization and metastasis of gastric cancer cells. Through molecular, cellular, animal, and clinical aspects, We will study the upstream and downstream mechanisms for Ephrin A1 regulating EMT plasticity of gastric cancer cells, elucidate its function in promoting tumor cell extravasation and maintaining stemness, thereby promoting the metastasis of gastric cancer cells. This subject will help to understand the molecular mechanism of distant metastasis of gastric cancer, and provide a new theoretical basis and potential molecular targets for treating gastric cancer metastasis.