title: Proteolysis in Helicobacter pylori-Induced Gastric Cancer.
abstract: Persistent infections with the human pathogen and class-I carcinogenHelicobacter pylori(H. pylori) are closely associated with the development of acute and chronic gastritis, ulceration, gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue (MALT) system. Disruption and depolarization of the epithelium is a hallmark ofH. pylori-associated disorders and requires extensive modulation of epithelial cell surface structures. Hence, the complex network of controlled proteolysis which facilitates tissue homeostasis in healthy individuals is deregulated and crucially contributes to the induction and progression of gastric cancer through processing of extracellular matrix (ECM) proteins, cell surface receptors, membrane-bound cytokines, and lateral adhesion molecules. Here, we summarize the recent reports on mechanisms howH. pyloriutilizes a variety of extracellular proteases, involving the proteases Hp0169 and high temperature requirement A (HtrA) of bacterial origin, and host matrix-metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and tissue inhibitors of metalloproteinases (TIMPs).H. pylori-regulated proteases represent predictive biomarkers and attractive targets for therapeutic interventions in gastric cancer.
authors.affiliation: Division of Microbiology, Department of Molecular Biology, Paris-Lodron University of Salzburg, Salzburg 5020, Austria. gernot.posselt@sbg.ac.at.
authors.forename: Gernot
authors.initials: G
authors.lastname: Posselt
authors.affiliation: Leeds Institute Biomedical and Clinical Sciences, St. James's University Hospital, University of Leeds, Leeds LS9 7TF, UK. j.crabtree@leeds.ac.uk.
authors.forename: Jean E
authors.initials: JE
authors.lastname: Crabtree
authors.affiliation: Division of Microbiology, Department of Molecular Biology, Paris-Lodron University of Salzburg, Salzburg 5020, Austria. silja.wessler@sbg.ac.at.
authors.forename: Silja
authors.initials: S
authors.lastname: Wessler
mesh_terms: D000818:Animals; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa; D010447:Peptide Hydrolases / Q000378:metabolism*; D059748:Proteolysis; D013274:Stomach Neoplasms / Q000209:etiology*
chemical_list: D010447:Peptide Hydrolases
keywords: ADAM; E-cadherin; EGFR; Helicobacter pylori; HtrA; MMP; TIMP; protease