title: Gastrokine 1 inhibits the carcinogenic potentials of Helicobacter pylori CagA.
abstract: 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.
authors.affiliation: Department of Pathology and.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of General Surgery, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Ho Suk
authors.initials: HS
authors.lastname: Seo
authors.affiliation: College of Pharmacy, Sahmyook University, Hwarangro 815, Nowon-gu, Seoul 139-742, South Korea.
authors.forename: Sung Sook
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Chae
authors.affiliation: Department of Pathology and.
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Pathology and.
authors.forename: Olga
authors.initials: O
authors.lastname: Kim
authors.affiliation: Department of Medicine, Howard University, Washington, DC 20060, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.affiliation: Department of Internal Medicine, Meharry Medical College, Nashville, TN 37208, USA and.
authors.forename: Duane T
authors.initials: DT
authors.lastname: Smoot
authors.affiliation: Department of Pathology and Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.affiliation: Department of Pathology and Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pathology and Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea wonsang@catholic.ac.kr.
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D036361:Peptide Hormones / Q000235:genetics*; D017382:Reactive Oxygen Species; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C477000:GKN1 protein, human; D036361:Peptide Hormones; D017382:Reactive Oxygen Species; C080866:cagA protein, Helicobacter pylori