FB2026_03 , released September 17, 2026
Human Disease Model Report: cancer, gastrointestinal, susceptibility due to H. pylori infection
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General Information
Name
cancer, gastrointestinal, susceptibility due to H. pylori infection
FlyBase ID
FBhh0001144
Disease Ontology Term
Parent Disease
OMIM
Overview

Infection with Helicobacter pylori appears to increase the risk of developing gastrointestinal cancers. Strains of H. pylori carrying the CagA (Cytotoxin-associated gene A) gene correlate with higher risk.

Multiple UAS constructs of the H. pylori CagA gene (Hpyl\cagA) have been introduced into flies and were initially used to characterize the biochemical impact of Hpyl\cagA expression within infected cells.

Early work in flies addressing the role of H. pylori in development of cancer involved Hpyl\cagA expressed in the developing eye disc, used as a model epithelial tissue. When Hpyl\cagA is expressed in a subset of cells within the eye disc epithelium, it disrupts tissue integrity and induces apoptosis through activation of JNK signaling. The genetic context of both the host cells in which Hpyl\cagA is expressed and their neighboring cells changes effects of Hpyl\cagA. Hpyl\cagA coexpressed with activated Ras85D results in enhanced tumor growth, compared to activated Ras85D alone.

More recent work using Drosophila intestinal stem cells (ISC) has found that expression of Hpyl\cagA in the ISC causes excessive cell proliferation and immune activation, and that it also impacts the microbiome of Hpyl\cagA-expressing animals. Expression of Hpyl\cagA in intestinal stem cells results in a cell-autonomous increase in cell proliferation, independent of the presence of a resident microbiota. An additional level of excessive cell proliferation is observed that is mediated through the altered microbiota that assembles specifically in the Hpyl\cagA-expressing adult midgut.

[updated Nov. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, gastrointestinal, susceptibility due to H. pylori infection
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Helicobacter pylori is a common gastric pathogen that can cause chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer (Wroblewski, et al, 2010; pubmed:20930071).

Genetics
Cellular phenotype and pathology

Once established, gastric cancer cells do not require H. pylori and CagA for maintaining their transformed phenotype; this is described as a hit-and-run mechanism (Hatakeyama 2017; pubmed:28413197).

Infection with H. pylori cagA-positive strains provokes strong inflammatory responses in the stomach mucosa (Hatakeyama 2017; pubmed:28413197).

Molecular information

Epidemiologic evidence suggests that infection with cagA-positive strains is especially associated with an increased risk of non-cardia gastric cancer (https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet).

External links
    Disease synonyms
    Ortholog Information
    Human gene(s) in FlyBase
      Other mammalian ortholog(s) used
        D. melanogaster Gene Information (1)
        Gene Snapshot
        Ras oncogene at 85D (Ras85D) encodes a protein that acts downstream of several cell signals, most notably from Receptor Tyrosine Kinases, to regulate tissue growth and development. When abnormally activated it can direct developmental defects and tissue hyperplasia, mimicking aspects of human disease including Rasopathies and cancer, respectively. [Date last reviewed: 2019-03-14]
        Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        High-scoring ortholog of human genes KRAS, HRAS, and NRAS (many to many; multiple paralogs and orthologs in both species). Dmel\Ras85D shares 78-86% identity and 86-92% similarity with KRAS, HRAS, and NRAS; for these three human genes, Ras85D is the highest-scoring ortholog in Drosophila.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Other Genes Used: Viral, Bacterial, Synthetic (1)
        Summary of Physical Interactions (29 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        pull down, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        two hybrid, anti tag coimmunoprecipitation, autoradiography
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        gtpase assay, autoradiography
        anti tag coimmunoprecipitation, peptide massfingerprinting
        two hybrid, pull down, western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        two hybrid, anti tag coimmunoprecipitation, anti tag western blot, pull down
        pull down, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, Identification by mass spectrometry, pull down, covalent binding, western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (26 alleles)
        Models Based on Experimental Evidence ( 17 )
        Allele
        Disease
        Evidence
        References
        model of  cancer
        Modifiers Based on Experimental Evidence ( 19 )
        Allele
        Disease
        Interaction
        References
        model of  cancer
        is exacerbated by ITPUAS.F
        model of  cancer
        is ameliorated by InRGL00139
        is ameliorated by InRJF01183
        is ameliorated by InRJF01482
        is ameliorated by NetBΔ
        is ameliorated by NetBKK103672
        is ameliorated by unc-5MI04273
        is ameliorated by JraNIG.2275R
        is ameliorated by bskDN.UAS
        is ameliorated by bskHMS00777
        is exacerbated by hepAct.UAS
        is exacerbated by imdUAS.cGa
        is ameliorated by TimpUAS.cPa
        ameliorates  cancer
        model of  kidney cancer
        is ameliorated by Pka-C1B3
        is ameliorated by mTorΔP
        model of  cancer
        is exacerbated by Ptp61FΔ
        is exacerbated by exe1
        is exacerbated by M6W186stop
        is ameliorated by Ptip3804
        is exacerbated by p53UAS.cUa
        is ameliorated by Ilp8MI00727
        is exacerbated by Clbn1Q
        exacerbates  carcinoma
        model of  carcinoma
        is exacerbated by NkapGD11807
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Related mammalian, viral, bacterial, or synthetic transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        loss of function allele
        loss of function allele
        P-element activity
        amorphic allele - genetic evidence
        References (11)