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

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

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.

Keywords: Cancer stem cell; Gastric cancer; IQGAP3; Mucin phenotype; Spheroid.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Female
  • Follow-Up Studies
  • GTPase-Activating Proteins / metabolism*
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mucins / metabolism
  • Neoplastic Stem Cells / metabolism
  • Phenotype
  • Prognosis
  • RNA Interference
  • Retrospective Studies
  • Spheroids, Cellular / metabolism
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / metabolism*
  • Up-Regulation

Substances

  • GTPase-Activating Proteins
  • IQGAP3 protein, human
  • Membrane Proteins
  • Mucins