Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Department of Surgery, Yokohama City University, Yokohama, Japan.
Pathobiology. 2018;85(3):192-200. doi: 10.1159/000481890. Epub 2017 Nov 1.
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.
IQGAP3 protein expression was analyzed by immunohistochemistry in 165 GC cases. RNA interference was used to inhibit IQGAP3 expression in GC cell lines.
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.
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.
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。
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。
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。
这些结果表明 IQGAP3 在胃 CSCs 中发挥重要作用。IQGAP3 位于细胞膜上，使其成为 GC 的潜在治疗靶点。
