鼻咽癌远处转移是患者治疗失败的重要原因。EB病毒潜伏感染膜蛋白2A（LMP2A）是促进鼻咽癌侵袭转移的重要因素之一，可通过调控整合素β4（ITGβ4）的定位来实现。我们前期研究发现鼻咽癌细胞中LMP2A的表达可激活EGFR通路，并与细胞内钙离子含量和钙蛋白酶活性增加有关。而ITGβ4是钙蛋白酶的潜在作用底物。由此，我们提出假设：LMP2A可通过激活EGFR/钙离子/钙蛋白酶/ ITGβ4路径促进鼻咽癌细胞转移。在本研究中，我们将从组织水平探讨LMP2A表达与EGFR磷酸化、钙蛋白酶家族表达及活性的关联；利用体外细胞模型验证LMP2A通过激活EGFR，进而增加钙离子含量，以此激活钙蛋白酶的作用；并进一步探究钙蛋白酶依赖的ITGβ4剪切是否促使鼻咽癌细胞的转移。本研究结果将阐明LMP2A促进鼻咽癌转移的又一项新的分子机理，且为针对鼻咽癌转移治疗提供了新的靶点和基础数据。

Distant metastasis is an important reason for the treatment failure of patients with nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) encoded latent membrane protein 2A (LMP2A) is one of the main factors to promote metastasis of NPC, which could be realized by affecting the localization of integrin beta 4 (ITGβ4). In previous study, we found that the phosphorylation of EGFR, intracellular Ca2+ and calpain activity were increased in LMP2A expressing NPC cells. ITGβ4 has been shown as the potential substrate of calpains. These lead us to hypothesize that LMP2A might promote metastasis of NPC cells depend on EGFR/Ca2+/calpain/ITGβ4 axis. Here, we will analyze the correlation between LMP2A and EGFR phosphorylation, expression and enzymatic activity of calpains in NPC primary tumor tissues, respectively; will investigate the activation of calpains affected by LMP2A expression through activating EGFR, and subsequently increasing the amount of intracellular Ca2+ utilizing the in vitro cell model; and will explore role of calpain-dependent ITGβ4 cleavage in the metastasis of NPC cells. Our results would shed light on the new molecular mechanism of LMP2A in promoting the metastasis of NPC, and provide new targets and evidence for the treatment of NPC.