Glutamate from nerve cells promotes perineural invasion in pancreatic cancer by regulating tumor glycolysis through HK2 mRNA-m6A modification

Here, we firstly provided evidence that glutamate from the nerve cells could upregulate the expression of HK2 through mRNA m6A modification via NMDAR2B and downstream Ca²⁺ dependent CaMKII/ERK-MAPK pathway, enhance the glycolysis in PDAC cells, and ultimately promote PNI. In addition, the dual targeting nanoparticles we synthesized were verified to block PNI effectively in PDAC.