ArticleNature microbiology2016
Host SHP1 phosphatase antagonizes Helicobacter pylori CagA and can be downregulated by Epstein-Barr virus.
Article in Nature microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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.
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.
Who cites it
60 citing papers in PubMed, 90 citations in OpenAlex.
- Genotoxic Bacteria and Oncogenic Viruses in Colorectal Cancer: Evidence, Gaps, and a Proposed Interaction Model.International journal of molecular sciences · 2026Review
- Interplay between pathogen-mediated immune evasion and innate immune negative regulation in gastrointestinal tumors.Frontiers in immunology · 2026Review
- Association of Helicobacter pylori and Epstein-Barr virus co-infection in gastric cancer patients: a prospective analytical study.Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery · 2026Article
- Co-infection ofJournal of virology · 2025Article
- Helicobacter pylori, microbiota and gastric cancer - principles of microorganism-driven carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2025Review
- Microbial oncogenesis within the gastric niche: how the gastric microbiota influencesFrontiers in microbiology · 2025Review
- T4SEpp: A pipeline integrating protein language models to predict bacterial type IV secreted effectors.Computational and structural biotechnology journal · 2024Article
- The role of microRNAs in the gastric cancer tumor microenvironment.Molecular cancer · 2024Review
- Helicobacter pylori and Epstein-Barr virus infection in cell polarity alterations.Folia microbiologica · 2024Review
- The viral etiology of EBV-associated gastric cancers contributes to their unique pathology, clinical outcomes, treatment responses and immune landscape.Frontiers in immunology · 2024Review
- Novel therapeutic regimens againstFrontiers in microbiology · 2024Review
- Review
- IL-8 Secreted by Gastric Epithelial Cells Infected withViruses · 2023Article
- Epstein-Barr Virus Infection Is Associated with Elevated Hepcidin Levels.International journal of molecular sciences · 2023Article
- Gastric microbiota dysbiosis andFrontiers in microbiology · 2023Review
- Impact of the Helicobacter pylori Oncoprotein CagA in Gastric Carcinogenesis.Current topics in microbiology and immunology · 2023Article
- Clinical Pathogenesis, Molecular Mechanisms of Gastric Cancer Development.Current topics in microbiology and immunology · 2023Article
- Epstein-barr virus/Iranian journal of microbiology · 2022Article
- Development of Epstein-Barr virus-associated gastric cancer: Infection, inflammation, and oncogenesis.World journal of gastroenterology · 2022Review
- Tumor Molecular and Microenvironment Characteristics in EBV-Associated Malignancies as Potential Therapeutic Targets: Focus on Gastric Cancer.Current issues in molecular biology · 2022Review
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most if not all gastric cancers are associated with chronic infection of the stomach mucosa with Helicobacter pylori cagA-positive strains(1-4). Approximately 10% of gastric cancers also harbour Epstein-Barr virus (EBV) in the cancer cells(5,6). Following delivery into gastric epithelial cells via type IV secretion(7,8), the cagA-encoded CagA protein undergoes tyrosine phosphorylation on the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs initially by Src family kinases (SFKs) and then by c-Abl(9,10). Tyrosine-phosphorylated CagA binds to the pro-oncogenic protein tyrosine phosphatase SHP2 and thereby deregulates the phosphatase activity(11,12), which has been considered to play an important role in gastric carcinogenesis(13). Here we show that the SHP2 homologue SHP1 interacts with CagA independently of the EPIYA motif. The interaction potentiates the phosphatase activity of SHP1 that dampens the oncogenic action of CagA by dephosphorylating the CagA EPIYA motifs. In vitro infection of gastric epithelial cells with EBV induces SHP1 promoter hypermethylation, which strengthens phosphorylation-dependent CagA action via epigenetic downregulation of SHP1 expression. Clinical specimens of EBV-positive gastric cancers also exhibit SHP1 hypermethylation with reduced SHP1 expression. The results reveal that SHP1 is the long-sought phosphatase that can antagonize CagA. Augmented H. pylori CagA activity, via SHP1 inhibition, might also contribute to the development of EBV-positive gastric cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.