Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells.

ABSTRACT:

Background and aims

Oncogenic KRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma (PDAC). However, Kras mutation alone is insufficient to transform precancerous cells into metastatic PDAC. This study investigates how KRAS-mutated epithelial cells acquire the capacity to escape senescence or even immune clearance, thereby progressing to advanced PDAC.

Methods

Single-cell RNA sequencing and analysis of primary PDAC tumors were conducted. Genetically engineered pancreas-specific Kras-mutated, dual specificity phosphatase-2 (Dusp2) knockout mouse models were established. Human and mouse primary pancreatic cancer cell lines were used for in vitro assessment of cancer characteristics. Tumor progression was studied via pancreas orthotopic and portal

SUBMITTER: Wang CA 

PROVIDER: S-EPMC11742192 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature