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

 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 
 Nature Communications, Vol.5 : 44233, 2014 
Journal Title
 Nature Communications 
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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.
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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
김남희(Kim, Nam Hee) ORCID logo https://orcid.org/0000-0002-3087-5276
김신(Kim, Shin)
김현실(Kim, Hyun Sil) ORCID logo https://orcid.org/0000-0003-3614-1764
육종인(Yook, Jong In) ORCID logo https://orcid.org/0000-0002-7318-6112
이여송(Lee, Yeo Song)
이용찬(Lee, Yong Chan)
이윤미(Lee, Yoon Mi)
차소영(Cha, So Young) ORCID logo https://orcid.org/0000-0002-2810-3883
차용훈(Cha, Yong Hoon) ORCID logo https://orcid.org/0000-0003-1761-3260
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