%0 Journal Article
%T The Janus kinase 1 is critical for pancreatic cancer initiation and progression.
%A Shrestha H
%A Rädler PD
%A Dennaoui R
%A Wicker MN
%A Rajbhandari N
%A Sun Y
%A Peck AR
%A Vistisen K
%A Triplett AA
%A Beydoun R
%A Sterneck E
%A Saur D
%A Rui H
%A Wagner KU
%J Cell Rep
%V 43
%N 5
%D 2024 May 28
%M 38733583
暂无%R 10.1016/j.celrep.2024.114202
%X 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 KRASG12D-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 δ (C/EBPδ) as a biologically relevant downstream target of JAK1 signaling, which is upregulated in human PDAC. Reinstating the expression of C/EBPδ 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/EBPδ and may serve as a molecular target for PDAC prevention and treatment.