The significance of ENAH in carcinogenesis and prognosis in gastric cancer

Oncotarget. 2017 Aug 2;8(42):72466-72479. doi: 10.18632/oncotarget.19801. eCollection 2017 Sep 22.

Abstract

The ENAH gene, which encodes a member of the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family of proteins, is involved in the assembly of actin filaments required for cell adhesion and motility. Recent studies show overexpressed ENAH in several cancer types, and ENAH correlates with tumor invasiveness. This study aimed to investigate the expression and function of ENAH in primary gastric adenocarcinoma, and its prognostic significance. We found significantly increased mRNA (P = 0.0283) and protein (P = 0.0301) expression of ENAH in gastric cancer tissues. ENAH expression markedly associated with tumor size (P < 0.001), T stage (P < 0.001), N stage (P = 0.001), TNM stage (P < 0.001) and prognosis (P < 0.001). Cox regression analyses revealed ENAH expression as an independent predictor of overall survival (P = 0.019). We also analyzed data of 155 gastric cancer cases from The Cancer Genome Atlas (TCGA) and found that ENAH expression significantly correlated with age (P = 0.003), T stage (P = 0.023) and prognosis (P = 0.05). Furthermore, the function of ENAH in cell proliferation, colony formation, cell migration and invasion of gastric cancer cells was analyzed in vitro. Knockdown of ENAH expression suppressed cell proliferation, colony formation, cell migration and invasion in MKN45 cells. Conversely, overexpression of ENAH promoted cell proliferation, cell migration and invasion in MGC803 cells. Our research suggests that ENAH might play promoting functions in carcinogenesis and progression of gastric cancer, and may serve as a valuable prognostic marker for primary gastric adenocarcinoma patients.

Keywords: ENAH; expression; function; gastric adenocarcinoma; prognosis.