Figure 1.
Model of stem cell–derived gastric carcinogenesis. During gastric carcinogenesis, long-lived stem cells and their niche are activated and expanded in response to tissue injury and inflammation. Activated stem cells give rise to metaplasia and dysplasia after accumulation of genetic and epigenetic changes. During Barrett’s esophagus development, dysplasia can progress to cancer with high Notch expression, while metaplasia appears to be postmitotic and a distinct lineage with low Notch expression.46 Given that Barrett’s esophagus may originate from gastric cardia glands, this may be the case in gastric metaplasia/dysplasia development. Indeed, notch signaling has been shown to increase proliferation and decrease differentiation, and thus clearly regulate mucous cell phenotypes in the stomach.99, 100, 101, 102 Aberrant notch activation leads to hyperplasia and dysplasia both in the corpus and antrum.68, 101, 102 SPEM cells express TFF2, which inhibits cancer progression.54, 55