KRAS/ACTN4/p65-NR2A axis mediates glutamine-glutamate metabolic coupling between schwann cells and pancreatic cancer promoting perineural invasion

This study identifies a reciprocal glutamine-glutamate metabolic symbiosis between PDAC cells and SCs as a driver of PNI, orchestrated by KRAS-ACTN4-NF-κB signaling and glutamate-NR2A-ROS-NRF2 pathways. Disrupting this axis with V9302 and PEAQX offers a novel therapeutic strategy to target PDAC's metabolic adaptability and neurotrophic microenvironment.