{Reference Type}: Journal Article
{Title}: The Janus kinase 1 is critical for pancreatic cancer initiation and progression.
{Author}: Shrestha H;Rädler PD;Dennaoui R;Wicker MN;Rajbhandari N;Sun Y;Peck AR;Vistisen K;Triplett AA;Beydoun R;Sterneck E;Saur D;Rui H;Wagner KU;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 5
{Year}: 2024 May 28
暂无{DOI}: 10.1016/j.celrep.2024.114202
{Abstract}: 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.