MUC15 loss promotes perineural invasion in pancreatic cancer by activating the IGF1R/STAT3/NGF pathway - PubMed
7 hours ago
- #Pancreatic Cancer
- #IGF1R/STAT3 Pathway
- #Perineural Invasion
- MUC15 loss promotes perineural invasion (PNI) in pancreatic ductal adenocarcinoma (PDAC).
- PNI is a critical but poorly understood feature affecting PDAC prognosis.
- MUC15 loss activates the IGF1R/STAT3/NGF signaling axis, driving neural invasion.
- Reduced MUC15 weakens IGF1R interaction, decreasing ubiquitination and increasing phosphorylation, activating STAT3.
- STAT3 activation leads to NGF transcription and secretion, facilitating PNI.
- MUC15 loss also promotes epithelial-mesenchymal transition (EMT) and alters tumor microenvironment interactions.
- Pharmacologic IGF1R inhibition reverses PNI effects, suggesting a potential therapeutic strategy.
- Restoring MUC15 or targeting IGF1R/STAT3-NGF may limit PNI in pancreatic cancer.