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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 |
| |
| Submission date |
Mar 11, 2023 |
| Last update date |
Jun 26, 2024 |
| Contact name |
Kay-Uwe Wagner |
| E-mail(s) |
wagnerk@karmanos.org
|
| 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
|
| 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 |
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