Helicobacter pylori infection is a major driver of gastric cancer, with the CagA oncoprotein promoting chronic inflammation and epithelial injury. However, the overall picture of the cytokine–receptor pathways involved in this process remains unclear. To investigate how CagA modulates epithelial signaling, we generated cagA-deletion and cagA-complemented mutants of the gerbil-adapted TN2 strain and infected AGS gastric epithelial cells for 6–48 h. We also analyzed 85 gastric biopsy specimens fro