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-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.


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.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.
Hyun
H
Chang
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.|Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Nayoung
N
Kim
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Ji Hyun
JH
Park
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.
Ryoung Hee
RH
Nam
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.
Yoon Jeong
YJ
Choi
Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, South Korea.
Seon Mee
SM
Park
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.
Yoon Jin
YJ
Choi
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.
Hyuk
H
Yoon
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.
Cheol Min
CM
Shin
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea.|Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Dong Ho
DH
Lee
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D014408:Biomarkers, Tumor; C103937:PicB protein, Helicobacter pylori; D053773:Transforming Growth Factor beta1; D037521:Virulence Factors
EMT; Gastric cancer; H. pylori; TGF-β1; cagE