國家衛生研究院 NHRI:Item 3990099045/13628
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 12145/12927 (94%)
造访人次 : 908522      在线人数 : 1008
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧：
  • 您可在西文检索词汇前后加上"双引号"，以获取较精准的检索结果
  • 若欲以作者姓名搜寻，建议至进阶搜寻限定作者字段，可获得较完整数据
    •  进阶搜寻
    主页 ‧ 登入 ‧ 上传 ‧ 说明 ‧ 关于NHRI ‧ 管理 到手机版


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/13628


    题名: Krupple like factor 10 modulates stem cell phenotype of pancreatic adenocarcinoma via transcriptional regulation of Notch signal pathway
    作者: Tsai, YC;Chen, SL;Peng, SL;Cheng, KH;Jiang, SS;Chuang, SE;Hui-Ju, C
    贡献者: National Institute of Cancer Research
    摘要: Background: Pancreatic adenocarcinoma (PDAC) is known for its deregulated TGFβ signal pathway. Therapeutic strategy targeting TGFβ is controversial due to the dual role of TGFβ with anti-proliferation in early phase and pro-metastatic in late phase of cancer progression. KLF10, an early response gene of TGFβ, positively feedback the antiproliferative effect in cancer. Recent studies revealed KLF10 expression were suppressed epigenetically in various cancers including PDAC. In contrary to TGFβ, KLF10 transcriptionally suppress Slug and Sirtuin 6 to prevent metastasis in advanced PDAC. The role of KLF10 in regulating tumorigenesis and stem cell phenotype is still unknown. Materials and Methods: From 105 patients of resectable PDAC, KLF10 expression level was evaluated to be reduced in 62% of tumor specimens. Low KLF10 expression correlated with larger tumor size and rapid loco-regional recurrence. In murine model of Kras mutation (KC mice), additional depletion of KLF10 induced 57% of PDAC compared to 0% at 18 to 24 wk of age. PDAC cells were genetically manipulated with KLF10mRNA silencing (PDACshKLF10) or inducible overexpression (PDACoeKLF10). Using limiting dilution assay of tumor growth, and orthotopic tumor implantation, we found higher tumorigenic ability of PDACshKlf10 compared to that of wild type. The stem cell phenotypes of PDACshKLF10 and PDACoeKLF10 were confirmed by sphere formation assay and FACS analysis of surface markers including CD24/CD44, ESA/c-Met, CD47 and CD133. Results: Notch signal pathway was found to be significantly enhanced from microarray analysis of wild type versus PDACshKLF10 cells. The increased Notch signal molecules were confirmed in RNA and protein level in genetically manipulated PDAC cells as well as clinical tissue specimens. Using Chip-PCR and luciferase promoter assay, KLF10 was demonstrated to bind to the promoter of Notch receptor 1, 3, and 4. DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester), a Notch inhibitor, suppressed in vitro spheroid formation, cell surface expression of stem cell markers, and tumor growth of PDACshKLF10 in orthotopic murine model. We conclude that KLF10 modulates stem cell phenotype of PDAC by transcriptionally suppressing Notch signal pathway. Loss of KLF10 in PDAC patients leads to Notch signal activation, development of stem cell phenotype and tumor progression. Notch inhibition may reverse malignant growth of PDAC with reduced KLF10 expression.
    日期: 2021-07
    關聯: Cancer Research. 2021 Jul;81(13, Suppl.):Abstract number 2001.
    Link to: https://doi.org/10.1158/1538-7445.AM2021-2001
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000680263503065
    显示于类别:[常慧如] 會議論文/會議摘要
    [莊雙恩] 會議論文/會議摘要
    [江士昇] 會議論文/會議摘要

    文件中的档案:

    没有与此文件相关的档案.



    在NHRI中所有的数据项都受到原著作权保护.

    TAIR相关文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回馈