Targeting focal adhesions:Helicobacter pylori-host communication in cell migration

The human pathogen H. pylori colonizes the stomachs of more than 50% of the world's population. The molecular interaction between H. pylori and cells of the gastric epithelium is thought to be the major factor inducing inflammatory responses of the infected host, which can result in the development of the malignant diseases gastric cancer or lymphoma of the MALT (mucosa-associated lymphoid tissue) system [1]. The pathogenesis of H. pylori mainly depends on the exposure of several bacterial factors, including cytotoxin-associated gene A (CagA), the type IV secretion system (T4SS), vacuolating cytotoxin A (VacA), outer inflammatory protein A (OipA) and several adherence factors, to the host [2-4]. Due to their pivotal role in H. pylori pathogenesis, these factors are currently being intensively studied to elucidate how they induce specific host responses.Much interest has been focused on the pathogenic factor CagA, which is transported via the T4SS into the host cytoplasm where it activates signal transduction pathways leading to cancer-associated processes [5]. Once injected into the host cytosol, the Glu-Pro-Ile-Tyr-Ala sequences (EPIYA motifs) in the CagA protein (CagAPY) are successively phosphorylated by non-receptor tyrosine kinases of the Src and Abl families [6,7]. A direct causal link between CagAPY and in vivo oncogenesis has recently been demonstrated in transgenic mice expressing CagA. These mice developed gastric polyps and adenocarcinoma of the stomach and small intestine [8]. However, the detailed molecular mechanism of CagAPY action in infected cells is not completely understood, although the injected CagA might imitate eukaryotic adaptor proteins by recruiting host signaling factors into protein complexes, both in a phosphorylation-dependent and a phosphorylation-independent manner [9-11]. Indeed, by generating a transgenic Drosophila model, it has been demonstrated that CagA expression rescues photoreceptor development in the absence of the Drosophil