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Status |
Public on Jun 26, 2024 |
Title |
The Janus kinase 1 is critical for the postnatal development of the pancreas and cancer progression |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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/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 rescue the growth of JAK1-deficient tumorspheres. 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.
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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.
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Contributor(s) |
Shrestha H, Rädler PD, Wagner K |
Citation(s) |
38733583 |
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Submission date |
Mar 11, 2023 |
Last update date |
Jun 26, 2024 |
Contact name |
Kay-Uwe Wagner |
E-mail(s) |
wagnerk@karmanos.org
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Organization name |
Barbara Ann Karmanos Cancer Institute Wayne State University School of Medicine
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Department |
Department of Oncology
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Street address |
421 East Canfield, EL01TM
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City |
Detroit |
State/province |
MI |
ZIP/Postal code |
48201-1976 |
Country |
USA |
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Platforms (2) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA943409 |