Loss of polarity by Cdc42 depletion and oncogenic Kras activation in the mouse intestinal epithelia leads to a necrotizing enterocolitis (NEC)-like disease - PubMed
3 hours ago
- #intestinal epithelia
- #necrotizing enterocolitis
- #cell polarity
- Combined loss of polarity by Cdc42 depletion and oncogenic Kras activation in mouse intestinal epithelia leads to NEC-like disease.
- Phenotypic defects include weight loss, inflammation, epithelial necroptosis, and lethality due to disrupted intestinal stem cells and architecture.
- Single-cell transcriptomic analysis shows dysregulation of polarity machinery, inflammatory pathways, and necroptosis program.
- Suppression of YAP, IL-1, TNFα signaling, or necroptosis rescues intestinal pathology.
- Similar NEC-like phenotypes occur when Cdc42 loss and oncogenic Kras activation start from intestinal stem cells.
- Mechanism involves polarity-YAP-IL1/TNFα signaling-induced necroptosis due to Kras hyperactivation and polarity loss.