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Pancreatic STAT5 activation promotes KrasG12D- and inflammation- induced acinar-to-ductal metaplasia and pancreatic cancer

GSE254340 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/01/25 Platform GPL23479
Summary
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to its predilection for late-stage presentation. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its functional role in KRAS-driven pancreatic tumorigenesis remains unclear. We found that high levels of STAT5 in tumor cells were associated with a poorer prognosis in patients. The loss of Stat5 in acinar cells significantly reduced the development of acinar-to-ductal metaplasia (ADM) and PDAC lesions driven by KRAS mutation and pancreatitis. IL-22 signaling, induced by chronic inflammation, enhanced KRAS-mutant mediated STAT5 phosphorylation and the tumor-promoting function of IL-22 depends on the activation of STAT5. Chromatin immunoprecipitation assays revealed that STAT5 was directly bound to the promoters of ADM mediators HNF4a.
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Also filed as BioProject PRJNA1069765 and SRA study SRP486176. Searching any of these in the dataset finder brings you back here.

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