N-cadherin Adhesive Interactions Mechanically Modulate Phenotype of Pancreatic Stellate Cells via YAP-dependent Mechanosensing - PubMed
12 hours ago
- #YAP
- #N-cadherin
- #Pancreatic stellate cells
- N-cadherin adhesive interactions modulate pancreatic stellate cell (PSC) phenotype via YAP-dependent mechanosensing.
- Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma with cancer-associated fibroblasts (CAFs) derived from PSCs.
- Activated PSCs remodel the extracellular matrix (ECM), increasing stiffness and reinforcing activation via YAP nuclear localization.
- A PEG-based hydrogel system with RGD and HAVDI peptides was used to study matrix stiffness and N-cadherin ligation effects.
- HAVDI-mediated N-cadherin ligation reduced PSC contractility by disrupting actin cap formation and nuclear flattening, decreasing YAP nuclear localization.
- Mechanical reprogramming via cadherin signaling reversed PSC activation within a specific time window, dependent on stiffness and mechanical dosing history.
- This study suggests a new therapeutic approach for PDAC by mechanically modulating cadherin signaling to reprogram CAFs.