SRA

Inflammatory cytokines promote the development of pancreatic ductal adenocarcinoma (PDAC), but the functions of specific intracellular signaling mediators in this process are less well-defined. In this study, we discovered that the Janus kinase 1 (JAK1) is critical for the early postnatal growth of the exocrine pancreas. Using a ligand-controlled and pancreas-specific knockout in adult mice, we demonstrate that JAK1 deficiency prevents the formation of KRASG12D-induced pancreatic tumors, and we established that JAK1 is essential for the constitutive activation of STAT3 whose activation is a prominent characteristic of PDAC. We identified C/EBPd as a biologically relevant downstream target of JAK1 signaling, which is upregulated in human PDAC. Reinstating the expression of C/EBPd was sufficient to rescue the growth of JAK1-deficient tumorspheres. Collectively, the findings of this study suggest that JAK1 executes important functions of inflammatory cytokines through C/EBPd and may serve as a molecular target for PDAC prevention and treatment. Overall design: Comparative gene expression profiling analysis of RNA-seq data forsix isogenic pairs of mouse pancreatic cancer cell lines before and after Cre-mediated deletion of JAK1.