Fig.2

The "hit and run" mechanism posits a potential role for H. pylori in gastric carcinogenesis. The virulence factor VacA is internalized upon binding to cell surface receptors on host cells. This interaction initiates cell vacuolation and the subsequent release of cytochrome c from mitochondria within the cells, ultimately leading to cytotoxicity and cell death. The virulence factor CagA is translocated into the host cell through the T4SS. CagA drives cell hyperproliferation through three key mechanisms: It is phosphorylated by Src kinase, leading to the activation of mitogenic signaling pathways. CagA triggers the activation of c-Met and initiates the PI3K/Akt signaling cascade. CagA interacts with E-cadherin, disrupting the E-cadherin/β-catenin complex, thereby activating the Wnt signaling pathway. These pathways converge to induce the accumulation of β-catenin, which in turn may facilitate the overexpression of pro-oncogenic genes. The inhibition of PAR1b by CagA induces BRCAness, leading to double-strand breaks in the host cell. And CagL induces the separation of ADAM17 from α5β1 integrins, which subsequently mediates the inhibition of H, K-ATPase expression through NF-κB inhibitory binding, resulting in hyposecretion of gastric acid. This hypochlorhydria triggers gastric dysbiosis. The genetic instability and dysbiosis may replace H. pylori in maintaining subsequent tumor phenotype and promoting tumor progression