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Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity

Authors
 Da-Gyum Lee  ;  Hyun Sil Kim  ;  Yeo Song Lee  ;  Shin Kim  ;  So Young Cha  ;  Ichiro Ota  ;  Nam Hee Kim  ;  Yong Hoon Cha  ;  Dong Hyun Yang  ;  Yoonmi Lee  ;  Gyeong-Ju Park  ;  Jong In Yook  ;  Yong Chan Lee 
Citation
 NATURE COMMUNICATIONS, Vol.5 : 44233, 2014 
Journal Title
 NATURE COMMUNICATIONS 
Issue Date
2014
MeSH
Antigens, Bacterial/physiology* ; Bacterial Proteins/physiology* ; Biopsy ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Cells, Cultured ; Down-Regulation/physiology* ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Epithelial-Mesenchymal Transition/physiology* ; Gastritis/metabolism ; Gastritis/pathology ; Glycogen Synthase Kinase 3/metabolism* ; Helicobacter pylori/physiology* ; Humans ; Signal Transduction/physiology ; Snail Family Transcription Factors ; Stomach/metabolism ; Stomach/pathology ; Stomach Neoplasms/metabolism ; Stomach Neoplasms/pathology ; Transcription Factors/physiology*
Abstract
Cytotoxin-associated gene A (​CagA) is an oncoprotein and a major virulence factor of H. pylori. ​CagA is delivered into gastric epithelial cells via a type IV secretion system and causes cellular transformation. The loss of epithelial adhesion that accompanies the epithelial–mesenchymal transition (EMT) is a hallmark of gastric cancer. Although ​CagA is a causal factor in gastric cancer, the link between ​CagA and the associated EMT has not been elucidated. Here, we show that ​CagA induces the EMT by stabilizing ​Snail, a transcriptional repressor of ​E-cadherin expression. Mechanistically we show that ​CagA binds GSK-3 in a manner similar to Axin and causes it to shift to an insoluble fraction, resulting in reduced GSK-3 activity. We also find that the level of ​Snail protein is increased in H. pylori infected epithelium in clinical samples. These results suggest that H. pylori ​CagA acts as a pathogenic scaffold protein that induces a ​Snail-mediated EMT via the depletion of GSK-3.
Full Text
http://www.nature.com/ncomms/2014/140723/ncomms5423/full/ncomms5423.html
DOI
10.1038/ncomms5423
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Shin(김신)
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Lee, Yeo Song(이여송)
Lee, Yong Chan(이용찬) ORCID logo https://orcid.org/0000-0001-8800-6906
Lee, Yoon Mi(이윤미)
Cha, So Young(차소영) ORCID logo https://orcid.org/0000-0002-2810-3883
Cha, Yong Hoon(차용훈) ORCID logo https://orcid.org/0000-0003-1761-3260
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99201
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