Wu Jing, Chen Xue-hua, Wang Xin-qiong, Yu Yi, Ren Jian-min, Xiao Yuan, Zhou Tong, Li Pu, Xu Chun-di
Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic.
Oncotarget. 2015 May 20;6(14):11794-805. doi: 10.18632/oncotarget.3649.
ERp19, a mammalian thioredoxin-like protein, plays a key role in defense against endoplasmic reticulum stress. It belongs to the protein disulfide isomerize (PDI) family, whose members have been implicated in development of breast, ovarian and gastrointestinal cancers. However, the role of ERp19 in gastric cancer (GC) remains undefined. Therefore, we sought to investigate the expression and prognostic value of ERp19 in GC patients, and to explore the role of ERp19 in tumorigenicity. Expression of ERp19 in gastric tissues was assessed by immunohistochemical staining and real-time PCR in clinical samples of GC patients. Statistical analysis of clinical cases revealed that the expression levels of ERp19 were higher in tumor tissues than non-tumor tissues. And the level of ERp19 expression was correlated with tumor size, lymph node involvement and poor clinical prognosis. Furthermore, ERp19 knockdown dramatically suppressed gastric cancer cell growth, inhibited cellular migration/invasion and down regulated the phosphorylation of FAK and paxillin, whereas ERp19 over-expression reversed these changes. We conclude that ERp19 contributes to tumorigenicity and metastasis of GC by activating the FAK signaling pathway, and may function as an oncogene in GC. ERp19 may represent a new diagnostic and prognostic marker and a novel target for the treatment of GC.
ERp19是一种哺乳动物硫氧还蛋白样蛋白，在抵御内质网应激中起关键作用。它属于蛋白质二硫键异构酶（PDI）家族，该家族成员与乳腺癌、卵巢癌和胃肠道癌的发生发展有关。然而，ERp19在胃癌（GC）中的作用仍不明确。因此，我们试图研究ERp19在GC患者中的表达及预后价值，并探讨ERp19在肿瘤发生中的作用。通过免疫组织化学染色和实时PCR评估GC患者临床样本中胃组织中ERp19的表达。临床病例的统计分析显示，ERp19在肿瘤组织中的表达水平高于非肿瘤组织。且ERp19表达水平与肿瘤大小、淋巴结受累及不良临床预后相关。此外，敲低ERp19可显著抑制胃癌细胞生长，抑制细胞迁移/侵袭，并下调FAK和桩蛋白的磷酸化，而ERp19过表达则逆转了这些变化。我们得出结论，ERp19通过激活FAK信号通路促进GC的肿瘤发生和转移，可能在GC中作为癌基因发挥作用。ERp19可能代表一种新的诊断和预后标志物以及GC治疗的新靶点。
