NFATc1 integrates STAT3 inflammatory signals to promote Kras(G12D)-driven carcinogenesis in the pancreas.

ABSTRACT: 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 on

ORGANISM(S): Mus musculus

SUBMITTER: Marek Bartkuhn 

PROVIDER: E-GEOD-39969 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress