page 249, Churin et al. explain how this widespread bug turns tumors metastatic by corrupting a growth factor receptor.
H. pylori mobilizes infected epithelial cells on its course to pathogenicity. The authors now show that mobilization results from activation of the hepatocyte growth factor (HGF) receptor c-Met. During development and differentiation, HGF-induced activation of c-Met initiates cell migration events. Inhibition of c-Met expression by siRNA blocks H. pylori–induced motility. H. pylori corrupts c-Met signaling, however, by injecting host cells with the protein CagA. Binding of CagA to c-Met resulted in modulation of receptor activity and recruitment of PLCγ, a mediator of cell polarity necessary for motility. CagA–PLCγ interactions mobilized infected cells through an ERK-dependent MAP kinase pathway, as inhibitors of MAP kinases or PLCγ blocked motility.
Unlike the gastric tumor cell line, a polarized canine kidney cell line does scatter in response to HGF. H pylori also induced c-Met–mediated motility in these cells, but did so through a PI3K-dependent pathway rather than through PLCγ, indicating that the bug uses alternative routes to motility depending on the cell type. The authors hope to look at animal models next to determine whether inappropriate activation of c-Met and the resulting mobilization of gastric cells is responsible for increased incidences of metastatic cancers in H. pylori infections. ▪