Decoding intestinal metaplasia: a step towards understanding gastric tumourigenesis
Tissue epithelia maintain their lineage identity under normal conditions but occasionally undergo ‘reprogramming’ into another lineage—a phenomenon known as metaplasia. Notable examples include intestinal metaplasia (IM) of the gastric mucosa or gastro-oesophageal junction, squamous metaplasia in the lung or uterine epithelium, and acinar-to-ductal metaplasia in pancreatic acinar cells. At the molecular level, metaplasia arises from disruptions in transcription factor networks that dictate tissue identity. Similar disruptions are exploited in ‘direct reprogramming’ technologies, where overexpressing specific transcription factors converts fibroblasts into entirely different cell types. In metaplasia, however, such reprogramming occurs spontaneously, often triggered by chronic environmental stressors such as chemical exposure, microbial infections, inflammation or dietary factors. Among human metaplastic lesions, one of the best-studied examples is IM, which is characterised by the loss
