H. pylori CagL-Y58/E59 Prime Higher Integrin α5β1 in Adverse pH Condition to Enhance Hypochlorhydria Vicious Cycle for Gastric Carcinogenesis

Yeh, Yi Chun; Cheng, Hsiu Chi; Yang, Hsiao Bai; Chang, Wei; Sheu, Bor Shyang

doi:10.1371/journal.pone.0072735

Cited by 21 publications

(55 citation statements)

References 42 publications

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“…We observed that CLIC1 blocked ERK-phosphorylation and AKT-phosphorylation, and both had reduced levels in orthotopically xenografted tumors. Studies have shown that ITGαv may be involved in the regulation of the MAPK/ERK and PI3K/AKT pathways, affecting tumor apoptosis and metastasis [40, 42]. In our study, the expression of ITGαv was down-regulated, while at the same time, ERK-phosphorylation and AKT-phosphorylation were down-regulated after silencing CLIC1 .…”

Section: Discussionsupporting

confidence: 54%

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

Mao

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. Methods: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. Results: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGβ1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGβ1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. Conclusions: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways.

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Section: Discussionsupporting

confidence: 54%

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

Mao

Wang

et al. 2018

Cell Physiol Biochem

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“…(kDa)FunctionReference A. actinomycetemcomitans Leukotoxin (LtxA)114Targets leukocyte function antigen-1 on activated WBC triggering lysosomal-mediated cell death. 113 Cytolethal distending toxin (Cdt)31.5Inhibits macrophage phagocytosis and subverts cytokine production 114 C. pneumoniae (CPAF) chlamydial protease-like or proteasome-like activity factor70Disrupts host MHC antigen presentation 115, 116 E. corrodens Corrodecin (bacteriocin)23.6Potential role at the periodontal site 117 Hydrolytic enzymes (includes proline aminopeptidase, thiol-dependent haemolysin and esterase activities)–Proposed to act against proline residues in collagen, immunoglobulin and complement proteins 118 F. necrophorum Leukotoxin (LktA)335.9Virulence factor 49 F. nucleatum Fusolysin115– 119 H. pylori CagA oncoprotein132.4Virulence factor. Reprograms gastric epithelial cells 120 VacA exotoxin (Vacuolating cytotoxin A)88Virulence factor 121 HP-NAP (neutrophil activating protein)204Activates innate immunity 122 CagL Y58/E59 (amino acid polymorphisms)26.8Increases hypochlorhydria; disrupts cell membrane integrity 123 Hpn7Modulates cytokine secretion 46 Tip-α19.6Bacterial pathogenesis 124 H. pylori HP017534Virulence factor 125 HcpE(HP0235)39.4Virulence factor 126 DupA (Duodenal ulcer producing)20Virulence factor 50 HtrA (high t...…”

Section: Resultsmentioning

confidence: 99%

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients

Chhibber‐Goel

Singhal

Bhowmik

et al. 2016

npj Biofilms Microbiomes

131

100

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Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 (Campylobacter rectus, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella nigrescens) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations.

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“…The activity of T4SS mediated by H. pylori positively associated with the risk of gastric cancer [ 20 ]. Furthermore, we disclosed that H. pylori isolates with the cagL amino acid sequence polymorphism Y58E59 could exploit higher amounts of gastric integrin α5β1 to mediate stronger T4SS activity [ 39 , 40 ]. Namely, more toxic H. pylori isolates shall have mediated with higher gastric cancer risk via the host integrin α5β1 expressions.…”

Section: Discussionmentioning

confidence: 99%

Genomic single nucleotide polymorphisms in the offspring of gastric cancer patients predispose to spasmolytic polypeptide-expressing metaplasia after H. pylori infection

et al. 2015

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BackgroundGastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM).ResultsThere were 389 family relatives of 193 non-cardiac GCA and 173 duodenal ulcer patients (DU), received blood sampling for DNA collection. The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU. The children of GCA had higher allele frequencies of ITGA5-1160 T-carrier (P = 0.006, OR[95% CI] = 2.2[1.2-4]), ITGB1-1949 A-carrier (P = 0.047; OR[95% CI] = 2.8[1.4-5.3]), ITGB1 + 31804 C-carrier (P = 0.013; OR[95% CI] = 4.7[1.7-13.0]), IL-10-592 AA (P = 0.014; OR[95% CI] = 2.3[1.4-4.0]) and COX-2-1195 G-carrier (P = 0.019; OR[95% CI] = 1.7[0.9-3.2]) than DU. The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10−4), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016). Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10−4).ConclusionsThe SNPs of ITGA5-1160/ITGB1-1949/ ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA, or more specific to combine RUNX3 + 492/TFF2-308 as A-carrier/CC shall be host factor predisposing to gastric cancer during H. pylori infection, and serve as marker to identify high-risk subjects for H. pylori eradication.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-015-0121-7) contains supplementary material, which is available to authorized users.

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H. pylori CagL-Y58/E59 Prime Higher Integrin α5β1 in Adverse pH Condition to Enhance Hypochlorhydria Vicious Cycle for Gastric Carcinogenesis

Cited by 21 publications

References 42 publications

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients

Genomic single nucleotide polymorphisms in the offspring of gastric cancer patients predispose to spasmolytic polypeptide-expressing metaplasia after H. pylori infection

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