Refining the Correa Cascade: Gastric Stem Cell Plasticity, Niche Remodelling, and Parallel Pathways to Neoplasia - PubMed
4 hours ago
- #Gastric Cancer
- #Precancerous Progression
- #Stem Cell Plasticity
- The review updates the traditional Correa cascade of gastric cancer progression by integrating new findings on cellular heterogeneity, plasticity, and non-sequential pathways.
- Gastric homeostasis involves distinct stem and progenitor populations in different stomach regions, regulated by signaling pathways like Wnt, Notch, and BMP.
- Helicobacter pylori infection disrupts the stem cell niche through mechanisms involving cytotoxin-associated gene A and BMP signaling collapse, leading to region-specific precancerous changes.
- In the antrum, hyperproliferation and CDX2-dependent intestinal metaplasia progress to dysplasia with mutations in TP53, KRAS, and APC.
- In the corpus, oxyntic atrophy triggers isthmus expansion via WNT5A/YAP signaling and a tuft-cell-ILC2 circuit, resulting in spasmolytic polypeptide-expressing metaplasia (SPEM), with KrasG12D mutations enabling direct dysplasia formation.
- Metaplasia and dysplasia can arise as parallel cellular fates from various origins, including ATOH1-deficient pit cells and bone marrow-derived hybrids, without displacing the tissue-level Correa sequence.