循环肿瘤细胞（CTC）是一类存在于外周血中的肿瘤细胞，与肿瘤的远处转移密切相关；CTC存在上皮间质化（EMT）特点，EMT是肿瘤侵袭转移一个重要过程，结合CTC研究EMT机制，可以对恶性肿瘤侵袭转移获得更为全面的认识。在EMT调控过程中，外泌体可通过传递LncRNA在EMT表型调控中起到关键性作用，我们前期发现胃癌外周血外泌体源LncRNA ZEB2-AS1与CTC的EMT状态相关，上调LncRNA ZEB2-AS1可以诱导胃癌细胞的EMT，而且可能通过ceRNA功能调控PRRX1实现。关于LncRNA ZEB2-AS1在EMT中的作用和机制、外泌体源LncRNA ZEB2-AS1/PRRX1通路促进CTC EMT均未见报道。我们拟根据初步发现，以机制研究为出发点，动物模型、临床样本为落脚点，系统阐明外泌体介导LncRNA ZEB2-AS1/PRRX1通路促进CTC EMT的作用机理。

Circulating tumor cell (CTC) from primary cancers hold great potential that initiates distant metastasis. Although CTC are extraordinarily rare cancer cells, our established techniques effective for their detection and identification ensure us to analyze valuable biological information carried by them and to explore cellular signal pathways related to the blood-borne metastatic mechanism. Our previous studies have shown that CTC exhibited characteristics of epithelial-mesenchymal transition (EMT), and the number of CTC was positively associated with advanced stage of hepatocellular carcinoma. EMT has been considered as a critical process for tumor cells to gain invasive phenotype. Therefore, studies focusing on CTC’ research would achieve a more comprehensive spectrum of metastatic mechanism by combining with EMT-mediated metastasis. LncRNAs have been demonstrated to act as master regulators of some key players that are involved in many important biological pathways of EMT, exosomes may act as the intercellular communication by transmitting intracellular cargoes to confer LncRNAs to active EMT pathway. Our preliminary findings suggested that the expression level of peripheral exsomal LncRNA ZEB2-AS1 was correlated with the number of CTCs with EMT characteristic, also we found that LncRNA ZEB2-AS1 acted as a novel player in modulating tumor cell EMT through interacting with PRRX1. Based on our preliminary results, this project aims to systematically determine the essential in vitro and in vivo roles for LncRNA ZEB2-AS1/PRRX1 mediated EMT in gastric CTC formation and invasion, finally identifying the underlying mechanisms responsible for these observations. These novel results obtained from this work would reveal mechanistic insights to highlight the importance of lncRNA ZEB2-AS1/PRRX1 mediated EMT in gastric cancer CTC invasion, and provide promising intervention targets for lowering the incidence of metastasis among patients with gastric cancer.