NFATc4 Regulates Sox9 Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation

doi:10.1155/2016/5272498

科研成果详情

题名	NFATc4 Regulates Sox9 Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation
作者	Hessmann, Elisabeth 1; Zhang, Jin-San2,3; Chen, Nai-Ming 1; Hasselluhn, Marie 1; Liou, Geou-Yarh 4; Storz, Peter 4; Ellenrieder, Volker 1; Billadeau, Daniel D.2; Koenig, Alexander 1,2
发表日期	2016-12-31
发表期刊	STEM CELLS INTERNATIONAL 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	EPIDERMAL-GROWTH-FACTOR ; DUCTAL ADENOCARCINOMA ; FACTOR RECEPTOR ; ONCOGENIC KRAS ; EGF RECEPTOR ; DIFFERENTIATION ; OVEREXPRESSION ; PROGRESSION ; REGENERATION ; ACTIVATION
摘要	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.
资助项目	German Cancer Research Foundation [109423]; Wilhelm Sander Foundation [2013.037.1]; Center of Regenerative Medicine at the Mayo Clinic, Jacksonville; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA140182]; National Cancer Institute Pancreas SPORE grant [P50 CA102701]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P50CA102701] Funding Source: NIH RePORTER
出版者	HINDAWI LTD
出版地	LONDON
ISSN	1687-966X
EISSN	1687-9678
卷号	2016 页码:5272498
DOI	10.1155/2016/5272498
页数	11
WOS类目	Cell & Tissue Engineering
WOS研究方向	Cell Biology
WOS记录号	WOS:000371083800001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26697077
PMC记录号	PMC4677249
SCOPUSEID	2-s2.0-84949967577
通讯作者地址	[Koenig, Alexander]Department of Gastroenterology and Gastrointestinal Oncology,University Medical Center Göttingen,Robert-Koch Street 40,Göttingen,37075,Germany
Scopus学科分类	Molecular Biology;Cell Biology
引用统计	被引频次：31[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/8102
专题	药学院（分析测试中心）药学院（分析测试中心）_生物制药系_生物制药工程
通讯作者	Koenig, Alexander
作者单位	1.Department of Gastroenterology and Gastrointestinal Oncology,University Medical Center Göttingen,Robert-Koch Street 40,Göttingen,37075,Germany; 2.Schulze Center for Novel Therapeutics,Division of Oncology Research,Mayo Clinic,200 1st Street SW No. W4,Rochester,55905,United States; 3.School of Pharmaceutical Sciences and Key Laboratory of Biotechnology and Pharmaceutical Engineering,Wenzhou Medical University,Wenzhou, Zhejiang,China; 4.Department of Cancer Biology,Mayo Clinic Cancer Center,4500 San Pablo Road,Jacksonville,32224,United States
推荐引用方式 GB/T 7714	Hessmann, Elisabeth,Zhang, Jin-San,Chen, Nai-Ming,et al. NFATc4 Regulates Sox9 Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation[J]. STEM CELLS INTERNATIONAL,2016,2016:5272498.
APA	Hessmann, Elisabeth., Zhang, Jin-San., Chen, Nai-Ming., Hasselluhn, Marie., Liou, Geou-Yarh., ... & Koenig, Alexander. (2016). NFATc4 Regulates Sox9 Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation. STEM CELLS INTERNATIONAL, 2016, 5272498.
MLA	Hessmann, Elisabeth,et al."NFATc4 Regulates Sox9 Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation".STEM CELLS INTERNATIONAL 2016(2016):5272498.