Gastrokine 1 inhibits the carcinogenic potentials of Helicobacter pylori CagA

Jung H wan Yoon, Ho S uk Seo, Sung S ook Choi, Hyun S uk Chae, Won S eok Choi, Olga Kim, Hassan Ashktorab, Duane T. Smoot, Suk W oo Nam, Jung Y oung Lee, Won S ang Park

Research output: Contribution to journalArticle


Helicobacter pylori CagA directly injected by the bacterium into epithelial cells via a type IV secretion system, leads to cellular changes such as morphology, apoptosis, proliferation and cell motility, and stimulates gastric carcinogenesis. We investigated the effects of cytotoxin-associated gene A (CagA) and gastrokine 1 (GKN1) on cell proliferation, apoptosis, reactive oxygen species (ROS) production, epithelial-mesenchymal transition (EMT) and cell migration in CagA- or GKN1-transfected gastric epithelial cells and mucosal tissues from humans and mice infected with H.pylori. On the molecular level, H.pylori CagA induced increased cell proliferation, ROS production, antiapoptotic activity, cell migration and invasion. Moreover, CagA induced activation of NF-κB and PI3K/Akt signaling pathways and EMT-related proteins. In addition, H.pylori CagA reduced GKN1 gene copy number and expression in gastric cells and mucosal tissues of humans and mice. However, GKN1 overexpression successfully suppressed the carcinogenic effects of CagA through binding to CagA. These results suggest that GKN1 might be a target to inhibit the effects from H.pylori CagA.

Original languageEnglish (US)
Pages (from-to)2619-2629
Number of pages11
Issue number11
StatePublished - Nov 1 2014
Externally publishedYes


ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yoon, J. H. W., Seo, H. S. U., Choi, S. S. O., Chae, H. S. U., Choi, W. S. E., Kim, O., Ashktorab, H., Smoot, D. T., Nam, S. W. O., Lee, J. Y. O., & Park, W. S. A. (2014). Gastrokine 1 inhibits the carcinogenic potentials of Helicobacter pylori CagA. Carcinogenesis, 35(11), 2619-2629.