死亡受体DR5表达于肿瘤细胞膜表面，可以与肿瘤坏死因子相关凋亡诱导配体（TRAIL）结合诱导肿瘤细胞凋亡，但关于DR5在细胞核内的表达及功能尚未明确。我们前期研究发现：DR5在胃癌细胞核内高表达，与患者脉管癌栓、淋巴结转移、TNM分期以及预后不良呈正相关，体外实验敲低DR5分子可以抑制胃癌细胞转移。基于此我们提出科学假说：DR5在胃癌中具有“双刃剑”作用，其生物学功能与亚细胞定位相关，DR5通过importinβ1介导进入细胞核内，促进胃癌细胞侵袭转移。本研究将在前期工作基础上，①通过胃癌临床标本免疫组化分析DR5核表达与胃癌患者临床病理参数及生存预后的关系；②通过体内、体外试验明确DR5分子促进胃癌细胞侵袭转移作用；③验证并干扰核转运蛋白importinβ1与DR5的相互作用，阻断DR5向核内运输过程，探索细胞核内DR5对胃癌细胞侵袭转移的调控作用及其潜在分子机制。

TRAIL initiates apoptotic signals via binding to cell surface death receptor 5 (DR5). However, little is known about the molecular function of nuclear DR5. Our previous work has shown that high level of nuclear DR5 expression was positively correlated with lymphovascular invasion, lymph node metastasis, TNM stage and poor prognosis in gastric cancer patients. In vitro experiments further revealed that DR5 knockdown declined migration of gastric cancer cells. We hypothesized that DR5 modulated tumor biological behaviors depending on its subcellular location. We assumed that DR5 might regulate cell migration through importinβ1-mediated nuclear translocation. In this study, we will further explore the clinical significance of nuclear DR5 expression, and the role of nuclear DR5 in the regulation of metastatic characteristics and its molecular mechanisms. This might provide new clues of molecular mechanisms and therapeutic strategy on gastric cancer.