Proteolysis in Helicobacter pylori-Induced Gastric Cancer
Abstract
:1. Introduction: The Gastric Epithelium in Health and Disease
Helicobacter Pylori-Dependent Gastric Pathologies
2. Deregulation of Extracellular Host Proteases by H. pylori
2.1. A disintegrin and Metallopeptidase ADAM
2.2. Matrix Metalloproteinases MMP
2.2.1. H. pylori-Induced MMPs: The Collagenases MMP-1, MMP-8, and MMP-13
2.2.2. H. pylori-Induced MMPs: The Gelatinases MMP-2, and MMP-9
2.2.3. H. pylori-Induced MMPs: The Stromelysins MMP-3, MMP-10, and MMP-11
2.2.4. Matrilysin, Macrophage Metallo-Elastase, and Membrane-Type MMPs
2.3. Tissue Inhibitors of Metalloproteinases TIMPs
3. H. pylori Expresses Proteases Exhibiting a Direct Influence on the Integrity of the Epithelial Barrier Function
H. pylori HtrA Induced E-Cadherin Ectodomain Shedding
4. Concluding Remarks
Conflicts of Interest
References
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MMP Type | Subgroup | Members |
---|---|---|
Soluble MMPs | Collagenases | MMP-1, -8, -13 |
Gelatinases | MMP-2, -9 | |
Stromelysins | MMP-3, -10, -11 | |
Heterogeneous Group | MMP-7, -12, -26, -28 | |
Membrane anchored MMPs | MT-MMPs | MMP-14, -15, -16, -17, -24, -25, |
Protease | Putative Target | Inducing Factors | Involved Signalling Pathways | Cellular Response |
---|---|---|---|---|
ADAM-10 | E-cadherin, c-Met, Notch1 | H. pylori [39] | unknown | loss of AJ [ 47], stem-like phenotype in cancer stem cells [48] |
ADAM-17 | proTNF-α, TGF-α, HB-EGF | CagL, IL-8, LPS H. pylori cagPAI+/− [41] | Rac1, p38, EGFR transactivation via HB-EGF | pro-inflammtory response [ 41,42], reduces apoptosis [44] |
MMP-1 | vitronectin, fibronectin, collagen, proTNF-α, proIL-1β, proMMP-2, proMMP-9 | cagPAI, OipA, gastrin | PKC, JNK, Erk, p38 | migration through collagen matrices [ 62], activation of gelatinase-type MMPs [58] |
MMP-8, -13 | unknown | unknown | unknown | unknown |
MMP-2, -9 | ECM, type IV collagen | MMP-9: CagA * MMP-2: unknown | MMP-9: NF-κB, Erk MMP-2: unknown | neutrophil recruitment [ 67], invasive growth, angiogenesis [32,78] |
MMP-3 | unknown | pCagA *, IL-1 β | unknown | EMT [ 80], migration and invasion [85] |
MMP-10 | unknown | CagA * | EGFR, Src, Erk | Invasion [ 51] |
MMP-11 | unknown | unknown | unknown | IGF-1 production, proliferation, invasion [ 88] |
MMP-7 | proTNF-α, HB-EGF, E-cadherin, IGFBP5 | cagPAI, gastrin | NF-κB, MEK, p120 | EMT [ 93], migration, invasion [89], IGFII release [97] |
MMP-12 | unknown | unknown | unknown | macrophage transmigration, reduced angiogenesis [ 32] |
Hp0169 | Type I collagen | na | unknown | Colonization of Mongolian gerbils [ 114] |
HtrA | E-cadherin, fibronectin | na | unknown | Disruption of AJs, access to intercellular space [ 46,125] |
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Posselt, G.; Crabtree, J.E.; Wessler, S. Proteolysis in Helicobacter pylori-Induced Gastric Cancer. Toxins 2017, 9, 134. https://doi.org/10.3390/toxins9040134
Posselt G, Crabtree JE, Wessler S. Proteolysis in Helicobacter pylori-Induced Gastric Cancer. Toxins. 2017; 9(4):134. https://doi.org/10.3390/toxins9040134
Chicago/Turabian StylePosselt, Gernot, Jean E. Crabtree, and Silja Wessler. 2017. "Proteolysis in Helicobacter pylori-Induced Gastric Cancer" Toxins 9, no. 4: 134. https://doi.org/10.3390/toxins9040134