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Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer

机译:跨膜蛋白IQGAP3的过度表达与胃癌患者的患者存活不良有关

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Objective: Spheroid colony formation is a useful method of cancer stem cell (CSC) characterization. We previously showed that the IQ motif containing the GTPase-activating protein 3 gene (IQGAP3) is upregulated in spheroid body-forming gastric cancer (GC) cells compared with parental cells. We investigated IQGAP3 expression in GC. Methods: IQGAP3 protein expression was analyzed by immunohistochemistry in 165 GC cases. RNA interference was used to inhibit IQGAP3 expression in GC cell lines. Results: In nonneoplastic gastric mucosa, weak staining of IQGAP3 was observed in the foveolar epithelium, while GC tissue showed stronger, more extensive staining. Of the 165 GC cases, 34 (21%) were positive for IQGAP3 expression. GC cases positive for IQGAP3 were found more frequently in stage II/III/IV cases than in stage I cases. Univariate and multivariate analyses demonstrated that IQGAP3 expression is an independent prognostic classifier of GC patients. Both the number and size of the spheres formed by MKN-74 cells were significantly reduced by knockdown of IQGAP3. The phosphorylation of Akt and Erk1/2 was inhibited by knockdown of IQGAP3. Conclusion: These results suggest that IQGAP3 plays an important role in gastric CSCs. The location of IQGAP3 on the cell membrane makes it a potential therapeutic target for GC. (C) 2017 S. Karger AG, Basel
机译:目的:球形集落形成是一种有效的肿瘤干细胞(CSC)鉴定方法。我们之前的研究表明,与亲代细胞相比,球状体形成胃癌(GC)细胞中含有GTPase激活蛋白3基因(IQGAP3)的IQ基序上调。我们研究了IQGAP3在GC中的表达。方法:采用免疫组织化学方法分析165例胃癌组织中IQGAP3蛋白的表达。RNA干扰用于抑制GC细胞系中IQGAP3的表达。结果:在非肿瘤性胃粘膜中,在小凹上皮中观察到较弱的IQGAP3染色,而GC组织显示更强、更广泛的染色。在165例GC病例中,34例(21%)IQGAP3表达阳性。IQGAP3阳性的GC病例在II/III/IV期病例中比在I期病例中更常见。单变量和多变量分析表明,IQGAP3表达是GC患者的一个独立预后指标。通过敲除IQGAP3,MKN-74细胞形成的球体的数量和大小都显著减少。敲除IQGAP3可抑制Akt和Erk1/2的磷酸化。结论:这些结果表明IQGAP3在胃CSCs中起重要作用。IQGAP3在细胞膜上的位置使其成为GC的潜在治疗靶点。(C) 2017年巴塞尔S.卡格股份公司

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