Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An infection-activated redox switch in the lysosomal protease legumain promotes tumor growth

ABSTRACT: Oxidative stress is a hallmark of tumorigenic infections, yet the underlying oxidation events that contribute to tumor growth remain poorly understood. By using chemical proteomics to map cysteine reactivity in human gastric cells, we determined that infection with the cancer-causing bacterium Helicobacter pylori induces oxidation of the lysosomal protease legumain at Cys219. The site-specific loss of Cys219 reactivity dysregulates intracellular legumain processing and localization in H. pylori-infected cells and increases tumor growth and mortality in a xenograft model. These findings establish a link between cysteine oxidation and tumorigenic signaling during bacterial infection and underscore the importance of oxidative post-translational modifications in tumor growth.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human) Helicobacter Pylori J99 (campylobacter Pylori J99)

TISSUE(S): Gastric Adenocarcinoma Cell

DISEASE(S): Gastric Adenocarcinoma

SUBMITTER: Daniel Bak

LAB HEAD: Eranthie Weerapana

PROVIDER: PXD025841 | Pride | 2022-03-21

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

human H. pylori induced TAK1/TAB1 interactomics

Project description:Study of dynamic changes in TAK1/TAB1 complex formation after H. pylori infection in human epithelial cells

2017-12-06 | PXD007632 | Pride

Helicobacter pylori-induced changes in miRNA expression in human gastric epithelial cells

Project description:H. pylori infection of human gastric epithelial cells (GEC) represses H,K-ATPase alpha subunit (HK-alpha) gene transcription through NF-Kappa B p50 homodimer binding to HK-alpha promoter. The bacterial cagA and slt gene products have been implicated in HK-alpha repression, which facilitates gastric H. pylori colonization and may underlie transient clinical hypochlorhydria. We hypothesized that H. pylori also regulates H,K-ATPase expression post-transcriptionally by micro-RNA interaction with HK-alpha mRNA. Our microarray experiment examined the effect of infection by wildtype H. pylori infection or a delta-cagA H. pylori mutant on miRNA expression of human gastric cells (AGS). Our results indicate that H. pylori infection up-regulates GEC miRNAs that target the HK-alpha 3' UTR and block translation, and that CagA activity is implicated in the miRNA up-regulation. Three types of samples were generated for microarray analysis: 1) AGS cells infected with wildtype H. pylori; 2) AGS cells infected with cagA-deficient H. pylori; 3) a mock-infected sample, prepared as a control by combining total RNA from uninfected AGS cells with total RNA from wildtype H. pylori, with relative eukaryotic and prokaryotic RNA amounts matching those observed in infected samples, based on proportional ribosomal peak heights quantified by Bioanalyzer. Three experimental replicates were generated for each type of treatment.

2016-01-18 | E-GEOD-51306 | biostudies-arrayexpress

Transcriptional profiling of gastric epithelial cells infected with wild type or arginase-deficient Helicobacter pylori

Project description:We studied the differential gene expression in the gastric cell line AGS infected with wild type (WT) or arginase gene mutant (rocF) Helicobacter pylori (Hp). We found that the presence of the gene regulates the inflammatory responses in terms of IL8 and MIP-1B. We conclude that arginase may be involved in regulating inflammatory responses which improves the chances of survival against the human immune response. AGS cells were infected for 16 hours with WT, the rocF, or a complemented H. pylori strain (rocF+). The RNA was extracted with TRIzol, treated with DNAse I (both from invitrogen). cRNA was made with the Illumina TotalPrep RNA amplification Kit (ambion AMIL1791).

2013-06-15 | E-GEOD-39919 | biostudies-arrayexpress

24 hrs of AGS cells exposed to H. pylori

Project description:H. pylori Outer membrane phospholipase A (OMPLA) has been suggested to play a role in the virulence of this bacterium. The aim of this study was to profile the most significant cellular pathways and biological processes affected in gastric epithelial cells during 24 hours of H. pylori exposure, and to study the inflammatory response to OMPLA+ and OMPLA- H. pylori variants

2012-01-01 | E-MTAB-846 | biostudies-arrayexpress

Development of Helicobacter pylori microarrays to test pathogenicity of clinical isolates

Project description:To distinguish between Helicobacter pylori isolates that may cause greater disease in patients, we used whole genome expression profiling as a platform to study host-pathogen interactions and identify gene signatures associated with isolates from patients with higher cancer risk. Expression profiles were studied for 3 clinical isolates from a region of high gastric cancer incidence (PZ5056, PZ5080, PZ5086) in Colombia and 3 isolates from a region with low gastric cancer incidence in Colombia (PZ5004, PZ5024, PZ5026). Each experiment was done in triplicate by infecting monolayers of gastric epithelial cells for 1 hour with the isolates.

2013-08-05 | E-GEOD-41497 | biostudies-arrayexpress

Helicobacter pylori pathogenic mechanism

Project description:Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray in vitro culture cells and in vivo patients of the chronic abdominal complaint. In this study，the effects of H. pylori infection on host gene expression in the gastric antral mucosa of patients with chronic gastritis were examined. The gastric antral mucosa was obtained from a total of 6 untreated patients undergoing gastroscopic and pathologic confirmation of chronic superficial gastritis. Three patients infected by H. pylori and 3 patients uninfected were used to cDNA microarray experiment.

2012-04-29 | E-GEOD-30042 | biostudies-arrayexpress

Transcription profiling of cell lines in response to Helicobacter pylori lipopolysaccharide shows Tribbles 3 - a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide

Project description:This SuperSeries is composed of the following subset Series: GSE25146: Changes in gene expression in AGS cells in response to Helicobacter pylori lipopolysaccharide GSE25147: Changes in gene expression in MKN45 cells in response to Helicobacter pylori lipopolysaccharide GSE25148: Changes in gene expression in HEK-TLR2 cells in response to Helicobacter pylori lipopolysaccharide Refer to individual Series

2011-01-12 | E-GEOD-25155 | biostudies-arrayexpress

Changes in gene expression in AGS cells in response to Helicobacter pylori lipopolysaccharide

Project description:This study set out to identify global changes in gene expression in AGS gastric epithelial cells following 8 hours stimulation with 10 μg/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori. Microarray analysis was used to compare changes in gene expression between cells treated with 10 μg/ml H. pylori LPS and untreated cells at the same time point. Total RNA was harvested from AGS cells following treatment with LPS for 8h or untreated cells at the same time-point. 2 independent experiments were carried out. RNA was labelled and hybridized to GeneChips to analyse changes in gene expression.

2011-01-12 | E-GEOD-25146 | biostudies-arrayexpress

Helicobacter pylori colonization ameliorates glucose homeostasis in mice

Project description:Background: Helicobacter pylori has been shown to alter the secretion of gastric hormones that modulate body fat deposition. Since cag-positive H. pylori strains interact intimately with the host gastric epithelial cells and trigger higher inflammation than cag-negative strains, we hypothesized that gastric colonization with H. pylori strains without functional cagA ameliorates obesity and its complications by modulating gastric gene expression and inflammation. Methodology/Principal Findings: To test this hypothesis we examined the effects of gastric colonization on metabolic and inflammatory markers in mice infected with two isogenic strains of H. pylori: 26695 strain 98-325 (cagA+ wild-type) and its cag pathogenicity island (cagPAI) mutant strain 99-305, a knockout made by inserting a chloramphenicol resistance cassette. Only the cagPAI mutant decreased fasting blood glucose levels, improved glucose tolerance and suppressed weight gain in db/db mice and mice with diet-induced obesity. These effects were associated with increased gastric leptin levels, suppressed infiltration of macrophages, enhanced influx of regulatory T cells (Treg) in adipose tissue and suppressed gastric inflammation. Gene set enrichment analyses of gastric mucosal samples identified six differentially modulated pathways, including the Hedgehog signaling pathway that is associated with control of cellular proliferation and gastric carcinogenesis as well as the insulin signaling pathway. Conclusions/Significance: Gastric colonization with cagPAI-negative strains of H. pylori ameliorate obesity and inflammation by modulating gastric gene expression, suggesting that cag-negative H. pylori strains might be beneficial in ameliorating obesity and its co-morbidities. Gastric mucosa from three groups of mice: uninfected, infected with H. pylori 26695 strain 98-325 (cagA+ wild-type) or infected with H. pylori mutant strain 99-305 (lacking cag pathogenicity island; cagA-)

2010-11-13 | E-GEOD-21833 | biostudies-arrayexpress

The downstream gene expression of AnxA4 in AGS cells

Project description:AnxA4 expression is increased in H. pylori associated tumors. Moreover, in renal-cell cancer, AnxA4 increases tumor cell dissemination and promotes cell migration, and in colorectal cancer, it is identified as a potential diagnostic marker. How AnxA4 might be involved in tumorgenesis has remained unclear. Here, we compared the gene expression profiles between the cells transfected with pcDNA3.1 (+)/AnxA4 and control (empty vector) to study the downstream genes of AnxA4 using Exon array technique. Four samples are analyzed.

2012-12-20 | E-GEOD-33620 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data