EB病毒转膜蛋白LMP－1通过高表达SDF-1／CXCR7诱导细胞迁移和肿瘤转移

病毒相关肿瘤的研究已经证实，病毒基因可能作为癌基因通过与细胞内蛋白的相互作用，发挥着重要的功能，包括癌变。既往的研究已经阐释了潜伏状态的EB病毒相关蛋白LMP-1作为癌基因通过上调SDF-1和激活CXCR4／7促进细胞迁移和肿瘤转移。本研究的前期预实验结果已证实了淋巴瘤和鼻咽部癌中LMP－1和CXCR7高表达。相关研究也证实优势表达的CXCR7在SDF-1的激活下发挥着特殊作用，优势表达CXCR7通过激活Rho家族RAC1诱导细胞极化和迁移。在本研究中，我们假设LMP-1可能通过其特有的信号通路，调节新型受体CXCR7的高表达，并可能激活高表达的CXCR7, 持续影响肿瘤细胞的迁移活性。由于CXCR7在多数组织细胞中低表达，本课题将利用初步筛选的特异性阻滞CXCR7活性的一组化合物，进一步证实高表达CXCR7对肿瘤细胞迁移的作用，同时筛选通过抑制CXCR7而影响肿瘤转移的候选化合物。

Study on virus-associated cancers has confirmed that viral genes may act as oncogene that interacts with intracellular protein to play important roles in intracellular functions, including the development of cancer. Previous studies have preliminary interpretation of EB virus-associated latent membrane protein (LMP-1) as the oncogene that promotes cell migration and metastasis through the upregulation of SDF-1 and activation of CXR4/7. Results from preliminary experiments have confirmed high expression of LMP-1 and CXCR7 in virus-associated lymphoma and nasopharyngeal carcinoma. On the basis of our study before, we have demonstrated the special roles played by high CXCR7 expression under the activation of SDF-1 activation. Moreover, with its own signaling pathway, the high CXCR7 expression induces cell polarization and migration by activating RAC1 from the Rho family. In this study, we assume LMP-1 may use its unique signaling pathway to regulate the high expression of CXCR7, to activate CXCR7 with high expression, and to enhance the migration activity of tumor cells. Furthermore, since CXCR7 have low expression under physiological conditions, particularly in blood cells, we will use the candidate compounds of inhibition of CXCR7 from preliminary screening, through in vitro and in vivo experiments, to further confirm the unique role of CXCR7 in cell migration. In the meantime, we will screen for compounds to identify the CXCR7 inhibitors that have a particularly affect on tumor metastasis by the suppression of CXCR7.