Caudal type homeoboxes as a driving force in Helicobacter pylori infection-induced gastric intestinal metaplasia

ABSTRACT Helicobacter pylori (H. pylori), a common pathogenic bacterium in the stomach, has been demonstrated to be a major cause of gastric cancer (GC). The typical pathological evolution of H. pylori infection-induced GC involves development from gastric atrophy, via intestinal metaplasia (IM) and dysplasia, to intestinal-type GC. During this process, IM is considered to be an “irreversible point” that significantly increases the risk for GC. Therefore, the elucidation of the mechanism underlying IM is of great significance for the prevention and treatment of gastric mucosal carcinogenesis associated with H. pylori infection. Caudal type homeoboxes (CDXs) are transcription factors involved in intestinal differentiation establishment and the maintenance of normal intestinal mucosa and IM. H. pylori infection increases the expression of CDXs through epigenetic regulation, the nuclear factor-kappaB signaling pathway and its downstream proinflammatory factors, and the transforming growth factor-beta signaling pathway, leading to the progression from normal gastric mucosa to IM. However, the precise mechanisms of gastric intestinal metaplasia have not yet been fully elucidated. In this review, we focus on research progress revealing the functions of CDXs in H. pylori infection-induced IM, as well as the regulators modulating this process.

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