title: Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis.
abstract: Helicobacter pylori is a gastric bacterial pathogen that is etiologically linked to human gastric cancer. The cytotoxin-associated gene A (CagA) protein of H. pylori, which is delivered into gastric epithelial cells via bacterial type IV secretion, is an oncoprotein that can induce malignant neoplasms in mammals. Upon delivery, CagA perturbs multiple host signaling pathways by acting as an extrinsic scaffold or hub protein. On one hand, signals aberrantly raised by CagA are integrated into a direct oncogenic insult, whereas on the other hand, they engender genetic instability. Despite its decisive role in the development of gastric cancer, CagA is not required for the maintenance of a neoplastic phenotype in established cancer cells. Therefore, CagA-conducted gastric carcinogenesis progresses through a hit-and-run mechanism in which pro-oncogenic actions of CagA are successively taken over by a series of genetic and/or epigenetic alterations compiled in cancer-predisposing cells during long-standing infection with cagA-positive H. pylori.
authors.affiliation: Division of Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan. Electronic address: mhata@m.u-tokyo.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hatakeyama
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications* / Q000473:pathology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002273:Carcinogens; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori