Wnt/β-catenin, an oncogenic pathway targeted byH. pyloriin gastric carcinogenesis

Xiaowen Song,Na Xin,Wei Wang,Chenghai Zhao

doi:10.18632/oncotarget.5758

Abstract

A section of gastric cancers presents nuclear β-catenin accumulation correlated with H. pylori infection. H. pylori stimulate Wnt/β-catenin pathway by activating oncogenic c-Met and epidermal growth factor receptor (EGFR), or by inhibiting tumor suppressor Runx3 and Trefoil factor 1 (TFF1). H. pylori also trigger Wnt/β-catenin pathway by recruiting macrophages. Moreover, Wnt/β-catenin pathway is found involved in H. pylori-induced gastric cancer stem cell generation. Recently, by using gastroids, researchers have further revealed that H. pylori induce gastric epithelial cell proliferation through β-catenin. These findings indicate that Wnt/β-catenin is an oncogenic pathway activated by H. pylori. Therefore, this pathway is a potential therapy target for H. pylori-related gastric cancer.

Highlights

Wnt/β-catenin pathway, called canonical Wnt pathway, is crucial to embryo development and adult tissue homeostasis [1, 2]
Neither adenomatous polyposis coli (APC) mutation [23, 24] nor APC methylation [25] seemed to be involved in gastric cancer. These findings suggest that other factors are involved in Wnt/β-catenin activation in gastric cancers
Activation of epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)/Akt signaling resulted in glycogen synthase kinase 3β (GSK3β) suppression and β-catenin accumulation via vacuolating cytotoxin A (VacA) or outer inflammatory protein A (OipA) [41, 43, 44]. These observations indicate that intracellular pathways initiated by EGFR and c-Met converge at PI3K/Akt-GSK3β-βcatenin under H. pylori infection (Figure 3)

Summary

Introduction

Wnt/β-catenin pathway, called canonical Wnt pathway, is crucial to embryo development and adult tissue homeostasis [1, 2]. Activation of epidermal growth factor receptor (EGFR) can resist H. pylori-induced gastric epithelial cell apoptosis [18, 19]. Increasing evidence has indicated that Wnt/βcatenin pathway is implicated in H. pylori-induced gastric carcinogenesis. These findings suggest that other factors are involved in Wnt/β-catenin activation in gastric cancers. Infection with CagApositive H. pylori induced phosphorylation of c-Met and gastric epithelial cell proliferation [31, 32].

Results

Conclusion