An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness

doi:10.3389/fcell.2020.00287

科研成果详情

题名	An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness
作者	Quan, Mei-Yu1; Guo, Qiang1; Liu, Jiayu 2; Yang, Ruo 1; Bai, Jing 1; Wang, Wei1; Cai, Yaxin 2; Han, Rui 1; Lv, Yu-Qing3; Ding, Li 4; Billadeau, Daniel D.4; Lou, Zhenkun 4; Bellusci, Saverio 2,5; Li, Xiaokun1; Zhang, Jin-San1,4
发表日期	2020-05-07
发表期刊	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	FGFR SOX2 pancreatic cancer stemness sphere-formation assay
其他关键词	FIBROBLAST GROWTH-FACTORS ; MESENCHYMAL TRANSITION ; CELL ; SOX2 ; EXPRESSION ; GEMCITABINE ; PATHWAY ; AMPLIFICATION ; CONTRIBUTES ; INHIBITION
摘要	Cancer stemness is associated with high malignancy and low differentiation, as well as therapeutic resistance of tumors including pancreatic ductal adenocarcinoma (PDAC). Fibroblast growth factors (FGFs) exert pleiotropic effects on a variety of cellular processes and functions including embryonic stem cell pluripotency and cancer cell stemness via the activation of four tyrosine kinase FGF receptors (FGFRs). FGF ligands have been a major component of the cocktail of growth factors contained in the cancer stemness-inducing (CSI) and organoid culture medium. Although FGF/FGFR signaling has been hypothesized to maintain cancer stemness, its function in this process is still unclear. We report that inhibition of FGF/FGFR signaling impairs sphere-forming ability of PDAC in vitro, and knocking down FGFR1 and FGFR2 decreased their tumorigenesis abilities in vivo. Mechanistically, we demonstrated that SOX2 is down-regulated upon loss of FGFR signaling. The overexpression of SOX2 in SOX2-negative cells, which normally do not display stemness capabilities, is sufficient to induce spheroid formation. Additionally, we found that AKT phosphorylation was reduced upon FGFR signaling inhibition. The inhibition of AKT using specific pharmacological inhibitors in the context of CSI medium leads to the loss of spheroid formation associated with loss of SOX2 nuclear expression and increased degradation. We demonstrate that an FGFR/AKT/SOX2 axis controls cancer stemness in PDAC and therefore may represent an important therapeutic target in the fight against this very aggressive form of cancer.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472601, 81702912]; Wenzhou Medical University; Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [KFO309 P7, 268555672-SFB1213]; National Key R&D Program of China [2017YFA0506000]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	2296-634X
卷号	8 页码:287
DOI	10.3389/fcell.2020.00287
页数	15
WOS类目	Cell Biology ; Developmental Biology
WOS研究方向	Cell Biology ; Developmental Biology
WOS记录号	WOS:000536655600001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	32457900
PMC记录号	PMC7221133
SCOPUSEID	2-s2.0-85085219254
通讯作者地址	[Li, Xiaokun]School of Pharmaceutical Sciences and International Collaborative Center on Growth Factor Research,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Developmental Biology;Cell Biology
引用统计	被引频次：18[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/9966
专题	药学院（分析测试中心）附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_精准医学中心实验室卓越中心_国际生长因子研究院
通讯作者	Li, Xiaokun
作者单位	1.School of Pharmaceutical Sciences and International Collaborative Center on Growth Factor Research,Wenzhou Medical University,Wenzhou,China; 2.Institute of Life Sciences,Wenzhou University,Wenzhou,China; 3.Center for Precision Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 4.Division of Oncology Research and Schulze Center for Novel Therapeutics,Mayo Clinic,Rochester,United States; 5.Cardio-Pulmonary Institute,German Lung Center,Justus Liebig University Giessen,Giessen,Germany
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Quan, Mei-Yu,Guo, Qiang,Liu, Jiayu,et al. An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2020,8:287.
APA	Quan, Mei-Yu., Guo, Qiang., Liu, Jiayu., Yang, Ruo., Bai, Jing., ... & Zhang, Jin-San. (2020). An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 8, 287.
MLA	Quan, Mei-Yu,et al."An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 8(2020):287.