PLXDC2调控丝状伪足形成促进胃癌侵袭转移的机制研究  

Plexin-domain containing 2 promotes invasion and metastasis of gastric cancer by regulating filopodia formation

作　　者：吴彬 王俊杰 任志祥 刘佳佳 钱锋 WU Bin;WANG Junjie;REN Zhixiang;LIU Jiajia;QIAN Feng(Center of General Surgery,Center of Minimal Invasive Gastrointestinal Surgery,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学)第一附属医院全军普通外科中心,微创胃肠外科中心,重庆400038

出　　处：《陆军军医大学学报》2022年第8期774-781,共8页Journal of Army Medical University

基　　金：国家自然科学基金面上项目(81773074)。

摘　　要：目的 观察PLXDC2(plexin-domain containing 2)对胃癌侵袭转移的作用,并探讨其机制。方法 收集TCGA-STAD数据库中胃癌患者资料,统计分析PLXDC2表达与胃癌临床病理参数及患者预后的关系。构建PLXDC2敲低/过表达胃癌细胞,用Matrigel-transwell侵袭实验和小鼠腹膜转移模型评估PLXDC2对胃癌细胞侵袭转移能力的影响。Western blot、免疫荧光检测PLXDC2在胃癌中发挥作用的潜在机制。结果 PLXDC2在胃癌组织中高表达(P<0.05),表达水平与组织学分级(P<0.01)、TNM分期(P<0.05)和T分期(P<0.05)呈正相关关系,与患者预后呈负相关关系(P<0.05)。Cox回归表明PLXDC2是影响患者预后的独立危险因素(P<0.05)。沉默PLXDC2表达显著抑制胃癌细胞的体外侵袭(P<0.01)和体内转移(P<0.01)能力,而过表达PLXDC2后得到相反的结果。改变PLXDC2的表达相应地改变胃癌细胞中Cdc42的表达和丝状伪足的形成。结论 PLXDC2通过调控丝状伪足的形成促进胃癌细胞的侵袭转移,可作为胃癌潜在的预后标志物和治疗靶点。Objective To investigate the role of plexin-domain containing 2(PLXDC2) in regulating the invasion and metastasis of gastric cancer(GC) and explore its mechanism. Methods The data of GC cases were collected from The Cancer Genome Atlas Stomach Adenocarcinoma(TCGA-STAD) database, and the relationship between PLXDC2 expression and the clinicopathological parameters as well as the prognosis of GC patients were statistically analyzed. PLXDC2 knockdown and overexpression GC cell models were constructed respectively, then Matrigel-transwell invasion assay and mouse peritoneal metastasis model were performed to evaluate the effect of PLXDC2 on the invasion and metastasis of GC cells. Western blotting and immunofluorescence assay were also adopted to investigate the potential mechanism of PLXDC2 in GC. Results PLXDC2 was highly expressed in GC tissues(P<0.05), and its expression level was positively correlated with neoplasm histological grade(P<0.01), TNM stage(P<0.05) and T stage(P<0.05), while negatively with the prognosis of patients(P<0.05). Cox regression analysis identified PLXDC2 as an independent risk factor for prognosis(P<0.05). Silencing PLXDC2 significantly inhibited the invasion ability of GC cells in vitro(P<0.01) and metastasis in vivo(P<0.01), whereas overexpression of PLXDC2 obtained the opposite results. Moreover, the changes of PLXDC2 level correspondingly affected the expression of Cdc42 and the formation of filopodia in GC cells. Conclusion PLXDC2 promotes the invasion and metastasis of GC cells by regulating the formation of filopodia, and may act as a potential prognostic biomarker and therapeutic target for GC.

关 键 词：PLXDC2 胃癌 转移 丝状伪足 

分 类 号：R341[医药卫生—基础医学] R730.23