Pancreatic cancer-derived extracellular vesicles enhance chemoresistance by delivering KRAS^G12D protein to cancer-associated fibroblasts.

ABSTRACT: KRAS mutations are instrumental in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the efficacy of direct targeting of KRAS mutations to inhibit tumor development remains doubtful. It is therefore necessary to gain a deeper insight into the mechanism in which KRAS mutations influence the effectiveness of clinical treatments. In this study, KRAS^G12D protein was detected in cancer-associated fibroblasts (CAFs) from clinical samples of PDAC. In vitro experiments demonstrated that KRAS^G12D protein in CAFs was not expressed from its own mutant gene but was derived from the ingestion of tumor cell-derived extracellular vesicles (EVs). The presence of KRAS^G12D protein in CAFs resulted in enhanced proliferation and migratio

SUBMITTER: Liu X 

PROVIDER: S-EPMC11897769 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature