IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5423.html
   My bibliography  Save this article

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

Author

Listed:
  • Da-Gyum Lee

    (Yonsei University College of Medicine)

  • Hyun Sil Kim

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Yeo Song Lee

    (Yonsei University College of Medicine)

  • Shin Kim

    (Yonsei University College of Medicine)

  • So Young Cha

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Ichiro Ota

    (Nara Medical University)

  • Nam Hee Kim

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Yong Hoon Cha

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Dong Hyun Yang

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Yoonmi Lee

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Gyeong-Ju Park

    (The School of Dentistry, Dankook University)

  • Jong In Yook

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Yong Chan Lee

    (Yonsei University College of Medicine)

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.

Suggested Citation

  • 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, 2014. "Helicobacter pylori CagA promotes Snail-mediated epithelial–mesenchymal transition by reducing GSK-3 activity," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5423
    DOI: 10.1038/ncomms5423
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5423
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5423?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5423. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.