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| Status |
Public on Jun 30, 2014 |
| Title |
NFATc1 integrates STAT3 inflammatory signals to promote Kras(G12D)-driven carcinogenesis in the pancreas. |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Inflammatory transcription networks have been linked with the development of pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrate that NFATc1 is both necessary and sufficient to drive progression of KrasG12D-initiated PDAC, particularly in the context of inflammation. Significantly, nuclear NFATc1 accelerates PDAC development in KrasG12D mice, whereas conditional NFATc1 deletion or pharmacological inhibition attenuates inflammation-mediated carcinogenesis. Mechanistically, NFATc1 induces STAT3 expression, complex formation and signal integration in PDAC. Genome-wide ChIP-sequencing and expression analysis in cells derived from c.n.NFATc1;KrasG12D mice identified combinatorial NFATc1/STAT3 binding at chromatin enhancer sites and subsequent regulation of key molecules involved in oncogenic signaling, growth and inflammation. Together, this study supports the relevance of inflammatory transcription factor networks in pancreatic carcinogenesis and provides a theoretical platform for therapeutic targeting of NFATc1 nucleoprotein complexes in PDAC.
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| Overall design |
NFATc1 ChIP followed by high throughput sequencing in primary murine pancreatic cancer cells (referred to as NKC cells) derived from transgenic mice with pancreas-specific constitutive activation of NFATc1 and KrasG12D mutation in the presence or absence of STAT3 shRNA; 2 ChIP samples (scramble DNA and shSTAT3 DNA) and 1 unenriched input control from the same chromatin pool.
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| Contributor(s) |
Baumgart S, Bartkuhn M, Wolf E, Ellenrieder V |
| Citation(s) |
24694735 |
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| Submission date |
Aug 08, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Marek Bartkuhn |
| E-mail(s) |
marek.bartkuhn@gen.bio.uni-giessen.de
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| Organization name |
Justus-Liebig-University Giessen
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| Department |
Biomedical Informatics and Systems Medicine
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| Street address |
Aulweg 132
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| City |
Giessen |
| State/province |
Hessen |
| ZIP/Postal code |
35392 |
| Country |
Germany |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA172179 |
| SRA |
SRP014743 |
