ASIA unversity:Item 310904400/86921
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 94286/110023 (86%)
造訪人次 : 21656511      線上人數 : 433
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋


    請使用永久網址來引用或連結此文件: http://asiair.asia.edu.tw/ir/handle/310904400/86921


    題名: MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 promotes tumorigenesis and trastuzumab resistance in breast cancer.
    作者: Thirumurthi,;Thirumurthi, U.;Shen, J.;Shen, J.;Xia, W.;Xia, W.;LaBaff, A.M;LaBaff, A.M.;Wei, Y.;Wei, Y.;Li, C-W.;Li, C-W.;Chang, W-C.;Chang, W-C.;Chen, C-H.;Chen, C-H.;洪明奇*
    貢獻者: 生物科技學系
    日期: 2014
    上傳時間: 2014-11-07 06:50:56 (UTC+0)
    摘要: Sirtuin 6 (SIRT6) is associated with longevity and is also a tumor suppressor. Identification of molecular regulators of SIRT6 might enable its activation therapeutically in cancer patients. In various breast cancer cell lines, we found that SIRT6 was phosphorylated at Ser(338) by the kinase AKT1, which induced the interaction and ubiquitination of SIRT6 by MDM2, targeting SIRT6 for protease-dependent degradation. The survival of breast cancer patients positively correlated with the abundance of SIRT6 and inversely correlated with the phosphorylation of SIRT6 at Ser(338). In a panel of breast tumor biopsies, SIRT6 abundance inversely correlated with the abundance of phosphorylated AKT. Inhibiting AKT or preventing SIRT6 phosphorylation by mutating Ser(338) prevented the degradation of SIRT6 mediated by MDM2, suppressed the proliferation of breast cancer cells in culture, and inhibited the growth of breast tumor xenografts in mice. Overexpressing MDM2 decreased the abundance of SIRT6 in cells, whereas overexpressing an E3 ligase-deficient MDM2 or knocking down endogenous MDM2 increased SIRT6 abundance. Trastuzumab (known as Herceptin) is a drug that targets a specific receptor common in some breast cancers, and knocking down SIRT6 increased the survival of a breast cancer cell exposed to trastuzumab. Overexpression of a nonphosphorylatable SIRT6 mutant increased trastuzumab sensitivity in a resistant breast cancer cell line. Thus, stabilizing SIRT6 may be a clinical strategy for overcoming trastuzumab resistance in breast cancer patients.
    Copyright © 2014, American Association for the Advancement of Science.
    關聯: Science Signaling;7(336):ra71.
    顯示於類別:[生物科技學系] 期刊論文

    文件中的檔案:

    檔案 大小格式瀏覽次數
    index.html0KbHTML419檢視/開啟


    在ASIAIR中所有的資料項目都受到原著作權保護.

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