UBE2T-Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation-Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer - PubMed
7 days ago
- #Pancreatic Cancer
- #Immunotherapy
- #UBE2T
- UBE2T promotes p53 degradation, enhancing glycolysis in pancreatic ductal adenocarcinoma (PDAC).
- Excessive lactate from glycolysis leads to histone H3 lysine 18 lactylation (H3K18la) in cancer-associated fibroblasts (CAFs).
- Lactylation activates CAFs, causing extracellular matrix (ECM) densification and reduced immunotherapy efficacy in PDAC.
- UBE2T inhibition with pentagalloylglucose (PGG) disrupts lactate crosstalk, reduces ECM deposition, and increases CD8+ T cell infiltration.
- Combining PGG with anti-PD-1 therapy improves outcomes in PDAC models.
- Targeting UBE2T offers a potential strategy to enhance immunotherapy effectiveness in PDAC.