SLC6A14-mediated glutamine promotes SYTL4-CXCL8 axis activation to drive gemcitabine resistance and immune evasion in pancreatic cancer.

ABSTRACT: Chemoresistance remains a major challenge in pancreatic ductal adenocarcinoma (PDAC). Glutamine sustains drug resistance and shapes the immunosuppressive tumor microenvironment; however, the underlying mechanisms remain unclear. Identifying key regulators that drive both gemcitabine resistance and immune evasion is crucial for improving theapeutic outcomes in PDAC. Here we identified solute-carrier family 6 member 14 (SLC6A14) as the central regulator of glutamine metabolism that drives gemcitabine resistance. SLC6A14-mediated glutamine metabolism facilitated α-ketoglutarate production, activating mTOR/NF-κB signaling to upregulate PD-L1 expression, playing a central role in immune evasion. Moreover, SLC6A14 induced CXC motif chemokine ligand 8 secretion via synaptotagmin-like 4-mediated e

SUBMITTER: Kang HW 

PROVIDER: S-EPMC12800172 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature