Effects of<i>Helicobacter pylori</i>on the cadherin–catenin complex

Bebb, James R.; Leach, Lopa; Zaitoun, Abed; Hand, Neil M.; Letley, Darren P.; Thomas, Russell J.; Atherton, John C.

doi:10.1136/jcp.2006.036772

Cited by 32 publications

(24 citation statements)

References 32 publications

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“…Our study revealed molecular mechanisms by which cagA-positive H. pylori induces cytoplasmic/nuclear accumulation of b-catenin as reported previously (Franco et al, 2005). In contrast to our results, Bebb et al (2006) recently reported that infection of HT29 colon carcinoma cells with H. pylori (either cagA-positive or cagA-negative strain) led to a reduction in junctional expression of b-catenin without any increase in cytoplasmic or nuclear immunostaining. Unfortunately, the work did not provide experimental data that show translocation of CagA from H. pylori into HT29 cells, raising a possibility that H. pylori failed to deliver sufficient amounts of CagA into the host cells in their infection experiment.…”

Section: Discussionsupporting

confidence: 85%

Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

et al. 2007

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Infection with Helicobacter pylori cagA-positive strains is associated with gastric adenocarcinoma. Intestinal metaplasia is a precancerous lesion of the stomach characterized by transdifferentiation of the gastric mucosa to an intestinal phenotype. The H. pylori cagA gene product, CagA, is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases. Tyrosine-phosphorylated CagA specifically binds to and activates SHP-2 phosphatase, thereby inducing cell-morphological transformation. We report here that CagA physically interacts with E-cadherin independently of CagA tyrosine phosphorylation. The CagA/E-cadherin interaction impairs the complex formation between E-cadherin and b-catenin, causing cytoplasmic and nuclear accumulation of b-catenin. CagA-deregulated b-catenin then transactivates b-catenin-dependent genes such as cdx1, which encodes intestinal specific CDX1 transcription factor. In addition to b-catenin signal, CagA also transactivates p21 WAF1/Cip1 , again, in a phosphorylation-independent manner. Consequently, CagA induces aberrant expression of an intestinal-differentiation marker, goblet-cell mucin MUC2, in gastric epithelial cells that have been arrested in G1 by p21 WAF1/Cip1 . These results indicate that perturbation of the E-cadherin/b-catenin complex by H. pylori CagA plays an important role in the development of intestinal metaplasia, a premalignant transdifferentiation of gastric epithelial cells from which intestinal-type gastric adenocarcinoma arises.

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Section: Discussionsupporting

confidence: 85%

Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

et al. 2007

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“…Recent in vitro studies reported that H pylori released the serine protease HtrA, which opens cell‐to‐cell junctions through cleaving epithelial junctional proteins including occludin, claudin‐8, and E‐cadherin and allows H pylori to reach the basolateral membranes where it can inject CagA in polarized conventional cell monolayers . On the other hand, in vivo study of gastric biopsy specimens during chronic H pylori infection has shown no adverse effects on E‐cadherin and β‐catenin . E‐cadherin in our model was unchanged after infection consistent with finding using the vivo model .…”

Section: Discussionmentioning

confidence: 59%

Changes of tight junction and interleukin‐8 expression using a human gastroid monolayer model of Helicobacter pylori infection

et al. 2019

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Background Lack of a model that mirrors Helicobacter pylori‐induced gastric mucosal inflammation has hampered investigation of early host‐bacterial interactions. We used an ex vivo model of human stomach, gastric epithelial organoid monolayers (gastroid monolayers) to investigate interactions of H pylori infection and the apical junctional complex and interleukin‐8 (IL‐8) expression. Method Morphology of human antral mucosal gastroid monolayers was evaluated using histology, immunohistochemical (IHC) staining, and transmission electron microscopy (TEM). Functional and gross changes in the apical junctional complexes were assessed using transepithelial electrical resistance (TEER), cytotoxicity assays, and confocal laser scanning microscopy. IL‐8 expression was evaluated by real‐time quantitative PCR and ELISA. Results When evaluated by IHC and TEM, the morphology of gastroid monolayers closely resembled in vivo human stomach. Following inoculation of H pylori, TEER transiently declined (up to 51%) in an H pylori density‐dependent manner. TEER recovered by 48 hours post‐infection and remained normal despite continued presence and replication of H pylori. Confocal scanning microscopy showed minimal disruption of zonula occludens‐1 or E‐cadherin structure. IL‐8 production was unchanged by infection with either CagA‐positive or CagA‐negative H pylori and JNK and MEK inhibitors did not suppress IL‐8 production, whereas p38 and IKK inhibitor significantly did. Conclusion Human gastroid monolayers provide a model for experimental H pylori infection more consistent with in vivo human infections than seen with typical gastric epithelial cell lines. This ex vivo system should lead to better understanding of H pylori host‐pathogen interactions.

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“…Within this context, published work suggests that overexpression of CagA impairs the complex formation between the adherens junction protein E-cadherin and ␤-catenin (25), whereas another study shows that the E-cadherin-␤-catenin complex was only slightly affected in a CagA-independent manner in H. pylori-infected cells (55). Furthermore, it has been shown that CagA is dispensable for the disruption of adherens junctions or loss of adhesion (55,59).…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Suppresses Glycogen Synthase Kinase 3β to Promote β-Catenin Activity

Sokolova

Bożko

Naumann

2008

Journal of Biological Chemistry

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Effects ofHelicobacter pylorion the cadherin–catenin complex

Cited by 32 publications

References 32 publications

Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

Changes of tight junction and interleukin‐8 expression using a human gastroid monolayer model of Helicobacter pylori infection

Helicobacter pylori Suppresses Glycogen Synthase Kinase 3β to Promote β-Catenin Activity

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