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Proteolytic Landscapes in Gastric Pathology and Cancerogenesis

Gastric cancer is a leading cause of cancer-related death, and a large proportion of cases are inseparably linked to infections with the bacterial pathogen and type I carcinogen Helicobacter pylori. The development of gastric cancer follows a cascade of transformative tissue events in an inflammator...

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Autores principales: Bernegger, Sabine, Jarzab, Miroslaw, Wessler, Silja, Posselt, Gernot
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910283/
https://www.ncbi.nlm.nih.gov/pubmed/35269560
http://dx.doi.org/10.3390/ijms23052419
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author Bernegger, Sabine
Jarzab, Miroslaw
Wessler, Silja
Posselt, Gernot
author_facet Bernegger, Sabine
Jarzab, Miroslaw
Wessler, Silja
Posselt, Gernot
author_sort Bernegger, Sabine
collection PubMed
description Gastric cancer is a leading cause of cancer-related death, and a large proportion of cases are inseparably linked to infections with the bacterial pathogen and type I carcinogen Helicobacter pylori. The development of gastric cancer follows a cascade of transformative tissue events in an inflammatory environment. Proteases of host origin as well as H. pylori-derived proteases contribute to disease progression at every stage, from chronic gastritis to gastric cancer. In the present article, we discuss the importance of (metallo-)proteases in colonization, epithelial inflammation, and barrier disruption in tissue transformation, deregulation of cell proliferation and cell death, as well as tumor metastasis and neoangiogenesis. Proteases of the matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase domain-containing protein (ADAM) families, caspases, calpain, and the H. pylori proteases HtrA, Hp1012, and Hp0169 cleave substrates including extracellular matrix molecules, chemokines, and cytokines, as well as their cognate receptors, and thus shape the pathogenic microenvironment. This review aims to summarize the current understanding of how proteases contribute to disease progression in the gastric compartment.
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spelling pubmed-89102832022-03-11 Proteolytic Landscapes in Gastric Pathology and Cancerogenesis Bernegger, Sabine Jarzab, Miroslaw Wessler, Silja Posselt, Gernot Int J Mol Sci Review Gastric cancer is a leading cause of cancer-related death, and a large proportion of cases are inseparably linked to infections with the bacterial pathogen and type I carcinogen Helicobacter pylori. The development of gastric cancer follows a cascade of transformative tissue events in an inflammatory environment. Proteases of host origin as well as H. pylori-derived proteases contribute to disease progression at every stage, from chronic gastritis to gastric cancer. In the present article, we discuss the importance of (metallo-)proteases in colonization, epithelial inflammation, and barrier disruption in tissue transformation, deregulation of cell proliferation and cell death, as well as tumor metastasis and neoangiogenesis. Proteases of the matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase domain-containing protein (ADAM) families, caspases, calpain, and the H. pylori proteases HtrA, Hp1012, and Hp0169 cleave substrates including extracellular matrix molecules, chemokines, and cytokines, as well as their cognate receptors, and thus shape the pathogenic microenvironment. This review aims to summarize the current understanding of how proteases contribute to disease progression in the gastric compartment. MDPI 2022-02-22 /pmc/articles/PMC8910283/ /pubmed/35269560 http://dx.doi.org/10.3390/ijms23052419 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bernegger, Sabine
Jarzab, Miroslaw
Wessler, Silja
Posselt, Gernot
Proteolytic Landscapes in Gastric Pathology and Cancerogenesis
title Proteolytic Landscapes in Gastric Pathology and Cancerogenesis
title_full Proteolytic Landscapes in Gastric Pathology and Cancerogenesis
title_fullStr Proteolytic Landscapes in Gastric Pathology and Cancerogenesis
title_full_unstemmed Proteolytic Landscapes in Gastric Pathology and Cancerogenesis
title_short Proteolytic Landscapes in Gastric Pathology and Cancerogenesis
title_sort proteolytic landscapes in gastric pathology and cancerogenesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910283/
https://www.ncbi.nlm.nih.gov/pubmed/35269560
http://dx.doi.org/10.3390/ijms23052419
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