Abstract 3180: Gastrokine 1 inhibits Helicobacter pylori CagA-induced gastric carcinogenesis

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 mortality, and stimulates gastric carcinogenesis. We investigated the effects of CagA and GKN1 on cell proliferation, apoptosis, ROS production, epithelial-mesenchymal transition (EMT) and cell migration in CagA or GKN1 transfected gastric epithelial cells and tissues from humans and mice infected with H. pylori. We studied whether H. pylori CagA regulates gene copy number and expression of GKN1 in gastric cells and tissues of both humans and mice. On a molecular level, H. pylori CagA induced increased cell proliferation, ROS production, anti-apoptotic activity, and cell migration and invasion, and activation of NF-κB and PI3K/Akt signaling pathways and epithelial mesenchymal transition-related proteins. In addition, H. pylori CagA reduced GKN1 gene copy number and expression in gastric cells and tissues of humans and mice. However, GKN1 overexpression successfully suppressed these carcinogenic effects through directly binding to CagA. These study identifies GKN1 as pharmacological target that inhibits the development and progression of gastric cancers via suppression of H. pylori CagA-induced carcinogenic potential. Additionally, we propose that GKN1 is a potential diagnostic biomarker for H. pylori CagA status, gastritis and gastric cancers. Citation Format: Junghwan Yoon, WonSang Park, Won Seok Choi. Gastrokine 1 inhibits Helicobacter pylori CagA-induced gastric carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3180. doi:10.1158/1538-7445.AM2014-3180