| First Author | Shrestha H | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 5 | Pages | 114202 |
| PubMed ID | 38733583 | Mgi Jnum | J:349756 |
| Mgi Id | MGI:7658736 | Doi | 10.1016/j.celrep.2024.114202 |
| Citation | Shrestha H, et al. (2024) The Janus kinase 1 is critical for pancreatic cancer initiation and progression. Cell Rep 43(5):114202 |
| abstractText | Interleukin-6 (IL-6)-class inflammatory cytokines signal through the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and promote the development of pancreatic ductal adenocarcinoma (PDAC); however, the functions of specific intracellular signaling mediators in this process are less well defined. Using a ligand-controlled and pancreas-specific knockout in adult mice, we demonstrate in this study that JAK1 deficiency prevents the formation of KRAS(G12D)-induced pancreatic tumors, and we establish that JAK1 is essential for the constitutive activation of STAT3, whose activation is a prominent characteristic of PDAC. We identify CCAAT/enhancer binding protein delta (C/EBPdelta) as a biologically relevant downstream target of JAK1 signaling, which is upregulated in human PDAC. Reinstating the expression of C/EBPdelta was sufficient to restore the growth of JAK1-deficient cancer cells as tumorspheres and in xenografted mice. Collectively, the findings of this study suggest that JAK1 executes important functions of inflammatory cytokines through C/EBPdelta and may serve as a molecular target for PDAC prevention and treatment. |
