Abstract
Infection with the human microbial pathogen Helicobacter pylori is assumed to lead to invasive gastric cancer. We find that H. pylori activates the hepatocyte growth factor/scatter factor receptor c-Met, which is involved in invasive growth of tumor cells. The H. pylori effector protein CagA intracellularly targets the c-Met receptor and promotes cellular processes leading to a forceful motogenic response. CagA could represent a bacterial adaptor protein that associates with phospholipase Cgamma but not Grb2-associated binder 1 or growth factor receptor-bound protein 2. The H. pylori-induced motogenic response is suppressed and blocked by the inhibition of PLCgamma and of MAPK, respectively. Thus, upon translocation, CagA modulates cellular functions by deregulating c-Met receptor signaling. The activation of the motogenic response in H. pylori-infected epithelial cells suggests that CagA could be involved in tumor progression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Antigens, Bacterial / metabolism*
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Bacterial Proteins / metabolism*
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Carcinoma / metabolism
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Carcinoma / microbiology*
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Carcinoma / physiopathology
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Cell Division / genetics
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Cell Transformation, Neoplastic / metabolism*
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Enzyme Inhibitors / pharmacology
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GRB2 Adaptor Protein
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Helicobacter Infections / complications*
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Helicobacter Infections / metabolism
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Helicobacter Infections / physiopathology
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Helicobacter pylori / metabolism*
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Helicobacter pylori / pathogenicity
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Hepatocyte Growth Factor / metabolism
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Humans
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Phospholipase C gamma
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Phosphoproteins / metabolism
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Protein Transport / genetics
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Proteins / metabolism
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Proto-Oncogene Proteins c-met / metabolism*
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Signal Transduction / genetics
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Stomach Neoplasms / metabolism
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Stomach Neoplasms / microbiology*
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Stomach Neoplasms / physiopathology
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Tumor Cells, Cultured
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Type C Phospholipases / antagonists & inhibitors
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Type C Phospholipases / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Bacterial
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Bacterial Proteins
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Enzyme Inhibitors
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GAB1 protein, human
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GRB2 Adaptor Protein
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GRB2 protein, human
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Phosphoproteins
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Proteins
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cagA protein, Helicobacter pylori
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Hepatocyte Growth Factor
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Proto-Oncogene Proteins c-met
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Mitogen-Activated Protein Kinase 1
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Type C Phospholipases
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Phospholipase C gamma