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]
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).
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).
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).