An Insulin-Exosome-TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer - PubMed
4 days ago
- #Pancreatic Cancer
- #Therapeutic Resistance
- #Fibrosis
- Hyperinsulinemia is a risk factor for pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor progression and stromal remodeling.
- An insulin-exosome-TNFAIP8-STAT1 signaling axis is identified, associated with fibroblast remodeling and desmoplastic progression in PDAC.
- Insulin enhances secretion of TNFAIP8-enriched exosomes from PDAC cells via PI3K/AKT-RAB3A signaling.
- TNFAIP8 recruits TRIM21 to facilitate STAT1 ubiquitination and degradation, leading to myofibroblastic CAF features and increased extracellular matrix deposition.
- High TNFAIP8 expression correlates with fibrosis and poor prognosis in PDAC patients.
- TNFAIP8 silencing or shTNFAIP8 delivery reduces fibrosis, suppresses tumor progression, and enhances gemcitabine efficacy in orthotopic models.
- TNFAIP8 is proposed as a promising stromal-targeted therapeutic candidate for PDAC.