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Helicobacter pylori Might Induce TGF-β1-Mediated EMT by Means of cagE
Hyun Chang1, Nayoung Kim1,2, Ji Hyun Park2
1Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.
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-β1) is known to be carcinogenic and Helicobacter pylori is a predominant carcinogen of gastric cancer. Our study aimed to determine whether TGF-β1 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-β1 or H. pylori including cagE-negative (ΔcagE) 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-β1 or various strains of cagE-positive H. pylori, EMT-related marker altered significantly. However, the ΔcagE 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 ΔcagE mutant.
Conclusions:
EMT induction in gastric cancer cells by TGF-β1 was confirmed. Only infection with cagE-positive H. pylori upregulated the TGF-β1-mediated EMT pathway and consequently promotes EMT. Therefore, H. pylori might induce TGF-β1-mediated EMT associated with the cagE.
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