Posselt, G, Crabtree, JE and Wessler, S (2017) Proteolysis in Helicobacter pylori-Induced Gastric Cancer. Toxins, 9 (4). 134. ISSN 2072-6651
Abstract
Persistent infections with the human pathogen and class-I carcinogen Helicobacter 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 of H. 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 how H. pylori utilizes 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0). |
Keywords: | Helicobacter pylori; protease; MMP; ADAM; TIMP; E-cadherin; HtrA; EGFR |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Molecular Gastroenterology (Leeds) |
Funding Information: | Funder Grant number EU - European Union LSHC-CT-2005-018704 Yorkshire Cancer Research NOT GIVEN |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Apr 2017 11:12 |
Last Modified: | 10 Sep 2018 09:03 |
Published Version: | https://doi.org/10.3390/toxins9040134 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/toxins9040134 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115588 |