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.
| Original language | English |
|---|---|
| Article number | 4423 |
| Journal | Nature communications |
| Volume | 5 |
| DOIs | |
| Publication status | Published - 2014 Jul 23 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
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Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity. / Lee, Da Gyum; Kim, Hyun Sil; Lee, Yeo Song; Kim, Shin; Cha, So Young; Ota, Ichiro; Kim, Nam Hee; Cha, Yong Hoon; Yang, Dong Hyun; Lee, Yoonmi; Park, Gyeong Ju; Yook, Jong In; Lee, Yong Chan.
In: Nature communications, Vol. 5, 4423, 23.07.2014.Research output: Contribution to journal › Article
TY - JOUR
T1 - Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity
AU - Lee, Da Gyum
AU - Kim, Hyun Sil
AU - Lee, Yeo Song
AU - Kim, Shin
AU - Cha, So Young
AU - Ota, Ichiro
AU - Kim, Nam Hee
AU - Cha, Yong Hoon
AU - Yang, Dong Hyun
AU - Lee, Yoonmi
AU - Park, Gyeong Ju
AU - Yook, Jong In
AU - Lee, Yong Chan
PY - 2014/7/23
Y1 - 2014/7/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84904806601&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904806601&partnerID=8YFLogxK
U2 - 10.1038/ncomms5423
DO - 10.1038/ncomms5423
M3 - Article
C2 - 25055241
AN - SCOPUS:84904806601
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4423
ER -