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

Research output: Contribution to journalArticle

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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 languageEnglish
Article number4423
JournalNature communications
Volume5
DOIs
Publication statusPublished - 2014 Jul 23

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snails
Glycogen Synthase Kinase 3
Epithelial-Mesenchymal Transition
Cytotoxins
Helicobacter pylori
genes
Genes
Stomach Neoplasms
cancer
virulence
proteins
Complement Factor H
secretions
epithelium
causes
Oncogene Proteins
Pylorus
Snails
Virulence Factors
Cadherins

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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. / Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity. In: Nature communications. 2014 ; Vol. 5.
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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.",
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Lee, DG, Kim, HS, Lee, YS, Kim, S, Cha, SY, Ota, I, Kim, NH, Cha, YH, Yang, DH, Lee, Y, Park, GJ, Yook, JI & Lee, YC 2014, 'Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity', Nature communications, vol. 5, 4423. https://doi.org/10.1038/ncomms5423

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 journalArticle

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AU - Lee, Da Gyum

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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

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