HER-2相关食管-胃交界腺癌（AEG）易发生转移，是急需解决的难题。申请人前期发现PAQR3是胃癌的一个新的重要的抑癌基因，相关成果已发表在Ann Oncol上。但PAQR3在AEG中是否也发挥着抑癌基因的功能，尚不清楚。近期我们发现PAQR3在HER-2高表达的AEG组织中显著下调，与Twist表达显著负相关，是转移危险因素。在HER-2高表达的AEG细胞中过表达PAQR3可显著下调Twist表达、抑制EMT，并降低肿瘤转移能力；敲减HER-2可显著上调PAQR3和下调Twist表达。基于此我们提出PAQR3介导HER-2信号通路调控食管-胃交界腺癌转移这一假说。我们将从细胞、组织及动物三个层面，通过一系列体内和体外试验对PAQR3介导HER-2信号通路进行深入的功能及调控机制的研究，解析其发挥功能效应的途径及作用靶点，鉴定分子相互作用的精细模式。结果将为AEG靶向治疗提供新的思路。

The human epithelial growth factor receptor 2 (HER-2) related adenocarcinoma of esophagogastric junction (AEG) is easy to metastasis, becoming a problem needed to be solved urgently. We previously showed that PAQR3 is a new important tumor suppressor gene of gastric cancer. Related results have been published in Ann Oncol. However, its similar function in AEG isn’t yet definitive. Recently, we found that PAQR3 was obviously down-regulated in tumor tissue of AEG patients with HER-2 overexpression and negatively correlated to Twist, presenting a close relationship to tumor metastasis. Meanwhile, overexpression of PAQR3 in AEG cells with high HER-2 dramatically reduced Twist and suppressed EMT, sequentially impaired the ability of tumor metastasis. Knock down HER-2 increased the expression of PAQR3 but decreased Twist. Based the above results, we hypothesized that PAQR3 mediated HER-2 signal pathway to regulate AEG metastasis. In this study, we will investigate PAQR3-mediated HER-2 signal pathway and regulation mechanism in AEG in vivo and in vitro, to verify that the ways and targets of PAQR3-mediated function effect, to identify that the fine mode of molecular interaction. Our data may give an insight into AEG target therapy.