TY -的A2 -布鲁内利,西尔维亚AU - Hessmann,以利sabeth AU - Zhang, Jin-San AU - Chen, Nai-Ming AU - Hasselluhn, Marie AU - Liou, Geou-Yarh AU - Storz, Peter AU - Ellenrieder, Volker AU - Billadeau, Daniel D. AU - Koenig, Alexander PY - 2016 DA - 2015/11/30 TI - NFATc4 RegulatesSox9Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation SP - 5272498 VL - 2016 AB - Acinar transdifferentiation toward a duct-like phenotype constitutes the defining response of acinar cells to external stress signals and is considered to be the initial step in pancreatic carcinogenesis. Despite the requirement for oncogenic Kras in pancreatic cancer (PDAC) development, oncogenic Kras is not sufficient to drive pancreatic carcinogenesis beyond the level of premalignancy. Instead, secondary events, such as inflammation-induced signaling activation of the epidermal growth factor (EGFR) or induction of Sox9 expression, are required for tumor formation. Herein, we aimed to dissect the mechanism that links EGFR signaling to Sox9 gene expression during acinar-to-ductal metaplasia in pancreatic tissue adaptation and PDAC initiation. We show that the inflammatory transcription factor NFATc4 is highly induced and localizes in the nucleus in response to inflammation-induced EGFR signaling. Moreover, we demonstrate that NFATc4 drives acinar-to-ductal conversion and PDAC initiation through direct transcriptional induction of Sox9. Therefore, strategies designed to disrupt NFATc4 induction might be beneficial in the prevention or therapy of PDAC. SN - 1687-966X UR - https://doi.org/10.1155/2016/5272498 DO - 10.1155/2016/5272498 JF - Stem Cells International PB - Hindawi Publishing Corporation KW - ER -