Microbial Regulation of p53 Tumor Suppressor
Fig 2
Interaction between H. pylori and gastric epithelial cells results in cellular stress.
After adherence, H. pylori translocates CagA protein into host cells using the T4SS. Translocated CagA is rapidly tyrosine phosphorylated by host kinases c-Src and c-Abl and binds to SHP2 phosphatase, leading to alteration of intracellular signaling, including activation of multiple oncogenic pathways and cytoskeletal rearrangement [22]. H. pylori also produces VacA toxin, which binds to the cell surface and forms oligomers. VacA is internalized and forms anion-selective channels in the membranes of endocytic compartments, resulting in cell vacuolation. In addition, H. pylori compromises the integrity of the host genome by inducing oxidative DNA damage and DNA double-strand breaks [27,28]. Insert: An electron microphotograph of H. pylori attached to the surface of AGS human gastric epithelial cells. AGS cells were co-cultured with H. pylori strain 26695, and cag T4SS pili were visualized by scanning electron microscopy (white arrows).