Tight junction proteins: Gatekeepers turned facilitators in the pathogenesis of gastric adenocarcinoma

Figure 1 Factors contributing to the initiation and progression of gastric adenocarcinoma and metastasis. Oxidative stress, free radical induced injury, and Helicobacter pylori infection can trigger chronic inflammation, which in turn causes persistent DNA damage and activates multiple oncogenic pathways that drive carcinogenesis. Moreover, chronic inflammation and ulcer formation can disrupt the balance of gut microbiota, leading to dysbiosis and increased intestinal permeability (‘leaky gut’). This dysregulated microenvironment further promotes epithelial mesenchymal transition, thereby facilitating gastric cancer progression and metastasis. H. pylori: Helicobacter pylori.

Figure 2 Schematic illustration of the interplay among tight junctions, inflammation, gut microbiota, and gastric cancer progression. Helicobacter pylori infection triggers gastric inflammation by activating cytokine, nuclear factor kappa B, and signal transducer and activator of transcription 3 mediated inflammatory cascades, leading to tight junction disruption and increased intestinal permeability. The resulting leaky gut permits translocation of microbial toxins and inflammatory mediators, which promote epithelial mesenchymal transition and drive gastric carcinogenesis. IL: Interleukin; TNF: Tumor necrosis factor; NF-κB: Nuclear factor kappa B; STAT3: Signal transducer and activator of transcription 3; H. pylori: Helicobacter pylori; TJ: Tight junction; EMT: Epithelial mesenchymal transition.