CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly
CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly
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CD2AP通过促进细胞粘附和细胞骨架组装抑制胃癌转移
DOI：
10.1002/mc.23158
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发表时间：
2020-01-28
影响因子：
4.6
通讯作者：
Xue, Xiangyang
中科院分区：
文献类型：
--
作者：
Xie, Wangkai;Chen, Chao;Xue, Xiangyang
弥漫性胃癌（Diffuse gastric cancer，DGC）是一种缺乏有效系统治疗的恶性肿瘤。DGC的细胞骨架和细胞间粘附的改变是近年来DGC最具争议的研究结果之一。CD 2相关蛋白（CD 2AP）是调节细胞骨架组装和细胞间粘附的关键蛋白之一。然而，迄今为止，还没有研究CD 2AP在胃癌（GC）中的表达及其生物学意义。因此，本研究的目的是探讨CD 2AP的表达是否与胃癌的任何临床特征相关，并阐明其潜在的机制。620例患者组织标本的免疫组化结果表明，CD 2AP在DGC中表达下调。此外，低CD 2AP水平指示患者预后不良。在体外实验中，CD 2AP的强制表达导致GC细胞的迁移和侵袭显著减少，而CD 2AP的耗竭则具有相反的效果。免疫荧光分析表明，CD 2AP通过与F-肌动蛋白加帽蛋白CAPZA 1相互作用促进细胞粘附并影响细胞骨架组装。总体而言，上调CD 2AP可减弱GC转移，提示CD 2AP可作为GC患者预后和治疗的新生物标志物。
Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.