Evidence map›Paper›PMID 25123931›Full record

ArticleGut2015

Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells.

Lydia E Wroblewski, M Blanca Piazuelo, Rupesh Chaturvedi, Michael Schumacher, Eitaro Aihara, Rui Feng, Jennifer M Noto, Alberto Delgado, Dawn A Israel, Yana Zavros and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
13.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 137 citations in OpenAlex.

  1. Physical, chemical, and structural properties of human gastric organoid-derived mucus.American journal of physiology. Gastrointestinal and liver physiology · 2026
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  11. Clinical Pathogenesis, Molecular Mechanisms of Gastric Cancer Development.Current topics in microbiology and immunology · 2023
    Article
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  18. Article
  19. Human organoids in basic research and clinical applications.Signal transduction and targeted therapy · 2022
    Review
  20. Review

33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Lydia E WroblewskiDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
M Blanca PiazueloDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Rupesh ChaturvediDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Michael SchumacherDepartment of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, USA.
Eitaro AiharaDepartment of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, USA.
Rui FengDepartment of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, USA.
Jennifer M NotoDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Alberto DelgadoDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Dawn A IsraelDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Yana ZavrosDepartment of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, USA.
Marshall H MontroseDepartment of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, USA.
Noah ShroyerDivision of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
Pelayo CorreaDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Keith T WilsonDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Richard M PeekDivision of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Vanderbilt University · USUniversity of Cincinnati · USCincinnati Children's Hospital Medical Center · US

Funding

Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Role of Iron and B-Catenin Activation in Gastric CarcinogenesisP01CA116087 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2009 to 2026
$27.5M
Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Project 3 - Molecular Signatures of Gastric Carcinogenesis in the Host Response to H. pyloriP01CA028842 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 1985 to 2019
$15.8M
H.Pylori Relationship to Digestive Diseases and CancerR01CA077955 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2003 to 2026
$9.7M
Helicobacter Pylori and Gastrointestinal BiologyR01DK058587 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PEEK, RICHARD M. · 2001 to 2024
$7.8M
SENSING PH AT THE GASTRIC SURFACER01DK054940 · NIDDK · UNIVERSITY OF CINCINNATI · PI MONTROSE, MARSHALL H · 1999 to 2013
$4.3M
Immunomodulatory effects of arginine supplementation in colitis and colon cancerR01AT004821 · NCCIH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 2008 to 2017
$4.0M
The role of Hedgehog Signaling in gastric tissue repair and regenerationR01DK083402 · NIDDK · UNIVERSITY OF CINCINNATI · PI ZAVROS, YANA · 2011 to 2019
$3.7M
HPYLORI INDUCED DNA DAMAGE AND IMMUNE DYSREGULATIONR01DK053620 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 1997 to 2014
$3.4M
Targeted chemoprevention of gastric carcinogenesis in high risk populationsR01CA190612 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MORGAN, DOUGLAS, WILSON, KEITH T. · 2014 to 2018
$3.0M
Mechanism that regulate Helicobacter pylori-induced beta-caterin activationR01DK073902 · NIDDK · VANDERBILT UNIVERSITY · PI PEEK, RICHARD M. · 2006 to 2009
$1.2M
BLRD VA I01 BX001453NCCIH NIH HHS AT 007324NCCIH NIH HHS K01 AT007324NCCIH NIH HHS R01 AT004821NCI NIH HHS CA 028842NCI NIH HHS CA 116087NCI NIH HHS CA 153539NCI NIH HHS CA77955NCI NIH HHS F32 CA153539NCI NIH HHS P01 CA028842NCI NIH HHS P01 CA116087NCI NIH HHS R01 CA077955NCI NIH HHS R01 CA190612NCI NIH HHS R29 CA077955NIDDK NIH HHS DK 053620NIDDK NIH HHS DK 058404NIDDK NIH HHS DK 58587NIDDK NIH HHS P30 DK058404NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK053620NIDDK NIH HHS R01 DK054940NIDDK NIH HHS R01 DK058587NIDDK NIH HHS R01 DK073902NIDDK NIH HHS R01 DK083402
6 · The paper itself

Abstract

objectiveHelicobacter pylori strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which cag(+) strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host-H. pylori interactions in a preclinical model. We used gastroids to inform and direct in vitro studies to define mechanisms through which H. pylori modulates expression of the cancer-associated tight junction protein claudin-7.

designGastroids were infected by luminal microinjection, and MKN28 gastric epithelial cells were cocultured with H. pylori wild-type cag(+) strains or isogenic mutants. β-catenin, claudin-7 and snail localisation was determined by immunocytochemistry. Proliferation was assessed using 5-ethynyl-2'-deoxyuridine, and levels of claudin-7 and snail were determined by western blot and flow cytometry.

resultsGastroids developed into a self-organising differentiation axis and H. pylori induced mislocalisation of claudin-7 and increased proliferation in a CagA- and β-catenin-dependent manner. In MKN28 cells, H pylori-induced suppression of claudin-7 was regulated by β-catenin and snail. Similarly, snail expression was increased and claudin-7 levels were decreased among H. pylori-infected individuals.

conclusionsH. pylori increase proliferation in a strain-specific manner in a novel gastroid system. H. pylori also alter expression and localisation of claudin-7 in gastroids and human epithelial cells, which is mediated by β-catenin and snail activation. These data provide new insights into molecular interactions with carcinogenic potential that occur between H. pylori and epithelial cells within the gastric niche.

Indexed as

Animalsbeta CateninCell ProliferationCells, CulturedClaudinsCoculture TechniquesEpithelial CellsGastric MucosaHelicobacter InfectionsHelicobacter pyloriHumansMice, Inbred C57BLSnail Family Transcription FactorsTranscription Factorsbeta CateninClaudinsCldn7 protein, mouseCTNNB1 protein, mouseSnail Family Transcription FactorsTranscription FactorsCELL PROLIFERATIONGASTRIC CANCERGASTRIC INFLAMMATIONHELICOBACTER PYLORITIGHT JUNCTION

Identifiers

PMID25123931
PMCPMC4329117
OpenAlexW2164422245

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.