Fig. 4. Schematic representation of H. pylori CagA-directed “hit-and-run” gastric carcinogenesis.

When delivered into gastric epithelial cells, the H. pylori-derived CagA oncoprotein perturbs multiple intracellular signaling pathways, which promotes malignant transformation of the host cells. There is a mutual feedforward stimulatory mechanism between the oncogenic activities of CagA and the pro-inflammatory responses against cagA-positive H. pylori infection. The direct priming of pro-oncogenic signaling by CagA in the precancerous stage promotes the acquisition of genetic and epigenetic alterations that can compensate for the perturbed cell signaling by CagA. Therefore, the established gastric cancer cells no longer require CagA protein to maintain their malignant phenotypes.