Helicobacter pylori Might Induce TGF-β1-Mediated EMT by Means of cagE

Background: Epithelial-mesenchymal transition (EMT), in which polarized epithelial cells have mesenchymal cell phenotypes, is thought to be a key process of invasion and metastasis of cancer. Transforming growth factor beta-1 (TGF-beta 1) is known to be carcinogenic and Helicobacter pylori is a predominant carcinogen of gastric cancer. Our study aimed to determine whether TGF-beta 1 or H. pylori infection enhances EMT process and cytotoxin-associated gene E (CagE) is associated with EMT. Materials and Methods: Human gastric cancer cell AGS and MKN45 were treated with recombinant TGF-beta 1 or H. pylori including cagE-negative (DcagE) mutant. Besides the assessment of EMT-related markers expression levels by means of RT-qPCR, Western blot, and immunofluorescence assay, the induction of in vitro EMT on gastric cancer cells (AGS and MKN cell lines) was confirmed by wound-healing assay and invasion assay. Results: When gastric cancer cells were treated with TGF-beta 1 or various strains of cagE-positive H. pylori, EMT-related marker altered significantly. However, the DcagE mutant did not. Wound-healing assay and invasion assay showed enhanced migration ability of the cells treated with cagE-positive H. pylori but not in DcagE mutant. Conclusions: EMT induction in gastric cancer cells by TGF-beta 1 was confirmed. Only infection with cagE-positive H. pylori upregulated the TGF-beta 1-mediated EMT pathway and consequently promotes EMT. Therefore, H. pylori might induce TGF-beta 1-mediated EMT associated with the cagE.