WNT/β-catenin signaling: implications for homeostasis and tumorigenesis in the esophagus

The WNT/β-catenin signaling pathway plays a central role in the development, homeostasis, and tumorigenesis of the gastrointestinal tract. During embryonic development, dynamic regulation of β-catenin activity is essential for foregut formation and for the transition of the esophageal epithelium from columnar to stratified squamous morphology, with inhibitory signals ensuring proper lineage specification. In the adult esophagus, however, the precise role of WNT/β-catenin signaling in basal progenitor cell proliferation and differentiation remains incompletely understood, although dysregulation of this pathway, including overexpression of WNT ligands and downregulation of WNT inhibitors, has been observed in Barrett's esophagus (BE) and esophageal cancer. This review highlights recent insights into the roles of WNT signaling in esophageal development, epithelial homeostasis, and disease pathogenesis.