English  |  正體中文  |  简体中文  |  Items with full text/Total items : 93288/109022 (86%)
Visitors : 664776      Online Users : 426
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version

    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/64259

    Title: Targeting the EGFR/PCNA Signaling Suppresses Tumor Growth of Triple-Negative Breast Cancer Cells with Cell-Penetrating PCNA Peptides
    Authors: 余永倫;Yu, Yung-luen;鄒瑞煌;Chou, Ruey-Hwang;Liang, JH;Liang, JH;Chang, WJ;Chang, WJ;Su, KJ;Su, KJ;Tseng, YJ;Tseng, YJ;Huang, WC;Huang, WC;Wang, SC;Wang, SC;洪明奇;Hung, Mien-Chie
    Contributors: 生物科技學系
    Keywords: EPIDERMAL growth factor receptors;TYROSINE;GENE targeting;BREAST cancer;PHOSPHORYLATION;CANCER cells -- Proliferation;GENE expression;CELLULAR signal transduction
    Date: 2013-04
    Issue Date: 2013-10-29 10:55:12 (UTC+8)
    Abstract: Tyrosine 211 (Y211) phosphorylation of proliferation cell nuclear antigen (PCNA) coincides with pronounced cancer cell proliferation and correlates with poor survival of breast cancer patients. In epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant cells, both nuclear EGFR (nEGFR) expression and PCNA Y211 phosphorylation are increased. Moreover, the resistance to EGFR TKI is a major clinical problem in treating EGFR-overexpressing triple-negative breast cancer (TNBC). Thus, effective treatment to combat resistance is urgently needed. Here, we show that treatment of cell-penetrating PCNA peptide (CPPP) inhibits growth and induces apoptosis of human TNBC cells. The Y211F CPPP specifically targets EGFR and competes directly for PCNA tyrosine Y211 phosphorylation and prevents nEGFR from binding PCNA in vivo; it also suppresses tumor growth by sensitizing EGFR TKI resistant cells, which have enhanced nEGFR function and abrogated classical EGFR membrane signaling. Furthermore, we identify an active motif of CPPP, RFLNFF (RF6 CPPP), which is necessary and sufficient to inhibit TKI-resistant TNBC cell growth of orthotopic implanted tumor in mice. Finally, the activity of its synthetic retro-inverted derivative, D-RF6 CPPP, on an equimolar basis, is more potent than RF6 CPPP. Our study reveals a drug candidate with translational potential for the future development of safe and effective therapeutic for EGFR TKI resistance in TNBC.
    Relation: PLoS One
    Appears in Collections:[生物科技學系] 期刊論文

    Files in This Item:

    File SizeFormat

    All items in ASIAIR are protected by copyright, with all rights reserved.

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