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

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.