Oncogenic and tumor-suppressive forces converge on a progenitor niche at the benign-to-malignant transition - PubMed
4 hours ago
- #pancreatic cancer
- #spatial transcriptomics
- #tumor initiation
- The benign-to-malignant transition is a key step in cancer progression, studied in mouse models of pancreatic ductal adenocarcinoma (PDAC) with spontaneous p53 loss.
- In Kras-mutant cells, oncogenic and tumor-suppressive programs (e.g., p53, CDKN2A, SMAD4) co-activate in a progenitor-like population, triggering senescence-like responses.
- Spatial transcriptomic analysis shows the niche around these progenitor-like cells remodels stepwise during tumor progression, resembling invasive PDAC.
- Transient KRAS inhibition depletes progenitor-like cells and disrupts their niche, delaying malignancy initiation.
- p53 suppression promotes progenitor cell expansion, epithelial-mesenchymal reprogramming, and immune-privileged niche formation, highlighting this state as a convergence point for mutations and plasticity.