题名 | An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness |
作者 | |
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 | |
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. |
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