CagA protein of Helicobacter pylori: a hijacker of gastric epithelial cell signaling.
Epidemiological study has shown strong correlation between the Helicobacter pylori (H. pylori) infection and gastric carcinogenesis. However, the mechanism by which H. pylori induces gastric carcinogenesis is not known. In this review, we focused on the product of cytotoxin-associated gene A (CagA), one of the important virulence factors of H. pylori. H. pylori injects CagA protein into the host gastric epithelial cells through its needle-like structure, type IV secretion system. Injected CagA hijacks physiological signal transduction and causes pathological cellular response such as increased cell proliferation, motility, apoptosis and morphological change through different mechanisms. H. pylori has been shown to produce reactive oxygen species (ROS) in infected gastric mucosa. Although the main source of ROS production is possibly host neutrophil, we propose novel source of ROS production in this review; CagA itself can induce ROS production in gastric epithelial cell. Excessive ROS production in gastric epithelial cells can cause DNA damage and thus might involve in gastric carcinogenesis. Understanding the molecular mechanism by which H. pylori-induced carcinogenesis is important for developing new strategies against gastric cancer.
Handa
Osamu
O
Department of Biomedical Safety Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. handao@koto.kpu-m.ac.jp
Naito
Yuji
Y
Yoshikawa
Toshikazu
T
D000942:Antigens, Bacterial / Q000633:toxicity*; D001426:Bacterial Proteins / Q000633:toxicity*; D015197:Carcinogenicity Tests; D003603:Cytotoxins / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D041981:Gastrointestinal Tract / Q000166:cytology; D016480:Helicobacter pylori / Q000737:chemistry*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003603:Cytotoxins; D017382:Reactive Oxygen Species; C080866:cagA protein, Helicobacter pylori