跨膜蛋白 IQGAP3 的过表达与胃癌患者的不良生存相关。

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

机构信息

Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

Department of Surgery, Yokohama City University, Yokohama, Japan.

出版信息

Pathobiology. 2018;85(3):192-200. doi: 10.1159/000481890. Epub 2017 Nov 1.

DOI:10.1159/000481890

PMID:29131081

Abstract

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 non neoplastic 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.

摘要

目的

球体集落形成是一种鉴定癌症干细胞（CSC）的有用方法。我们之前的研究表明，与亲本细胞相比，富含 GTP 酶激活蛋白 3 基因（IQGAP3）的 IQ 基序在球体形成的胃癌（GC）细胞中上调。我们调查了 GC 中的 IQGAP3 表达。

方法

通过免疫组织化学分析 165 例 GC 病例中的 IQGAP3 蛋白表达。使用 RNA 干扰抑制 GC 细胞系中的 IQGAP3 表达。

结果

在非肿瘤性胃黏膜中，IQGAP3 在小凹上皮中呈弱阳性染色，而 GC 组织则表现出更强、更广泛的染色。在 165 例 GC 病例中，34 例（21%）表达 IQGAP3。与 I 期病例相比，IQGAP3 阳性的 GC 病例更常见于 II/III/IV 期病例。单因素和多因素分析表明，IQGAP3 表达是 GC 患者的独立预后分类器。IQGAP3 敲低后，MKN-74 细胞形成的球体数量和大小均显著减少。IQGAP3 敲低抑制 Akt 和 Erk1/2 的磷酸化。