...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuron >A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression
【24h】

A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression

机译：由机械敏感离子通道压电1和组织力学介导的前馈机制促使胶质瘤侵略

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Alteration of tissue mechanical properties is a physical hallmark of solid tumors including gliomas. How tumor cells sense and regulate tissue mechanics is largely unknown. Here, we show that mechanosensitive ion channel Piezo regulates mitosis and tissue stiffness of Drosophila gliomas, but not non-transformed brains. PIEZO1 is overexpressed in aggressive human gliomas and its expression inversely correlates with patient survival. Deleting PIEZO1 suppresses the growth of glioblastoma stem cells, inhibits tumor development, and prolongs mouse survival. Focal mechanical force activates prominent PIEZO1-dependent currents from glioma cell processes, but not soma. PIEZO1 localizes at focal adhesions to activate integrin-FAK signaling, regulate extracellular matrix, and reinforce tissue stiffening. In turn, a stiffer mechanical microenvironment elevates PIEZO1 expression to promote glioma aggression. Therefore, glioma cells are mechanosensory in a PIEZO1-dependent manner, and targeting PIEZO1 represents a strategy to break the reciprocal, disease-aggravating feedforward circuit between tumor cell mechanotransduction and the aberrant tissue mechanics.
机译：组织机械性能的改变是固体肿瘤的物理标志，包括胶质瘤。肿瘤细胞如何感觉和调节组织力学在很大程度上是未知的。在这里，我们表明机械敏感离子通道压电调节果蝇胶质瘤的丝分裂和组织刚度，但不是非转化的大脑。 Piezo1在激进的人胶质瘤中过表达，其表达与患者存活率相反。删除压电1抑制胶质母细胞瘤干细胞的生长，抑制肿瘤发育，延长小鼠存活。局灶性机械力激活来自胶质瘤细胞过程的突出的压电1依赖性电流，但不是SOMA。 Piezo1定位在局灶性粘连下，以激活整联蛋白 - FAK信号，调节细胞外基质，并加强组织加强。反过来，富有的机械微环境升高了压电1表达以促进胶质瘤的侵略。因此，胶质瘤细胞是压电1依赖性方式的机械感，并且靶向压电1表示破坏倾斜，肿瘤细胞机电扫描与异常组织力学之间的互殖疾病加重前馈回路的策略。

著录项

  • 来源
    《Neuron》 |2018年第4期|共24页
  • 作者

    Chen Xin; Wanggou Siyi; Bodalia Ankur; Zhu Min; Dong Weifan; Fan Jerry J.; Yin Wen Chi; Min Hyun-Kee; Hu Malini; Draghici Diana; Dou Wenkun; Li Feng; Coutinho Fiona J.; Whetstone Heather; Kushida Michelle M.; Dirks Peter B.; Song Yuanquan; Hui Chi-Chung; Sun Yu; Wang Lu-Yang; Li Xuejun; Huang Xi;

  • 作者单位

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Cent S Univ Xiangya Hosp Dept Neurosurg Changsha 410008 Hunan Peoples R China;

    Hosp Sick Children Program Neurosci &

    Mental Hlth Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Univ Toronto Dept Mech &

    Ind Engn Toronto ON M5S 3G8 Canada;

    Childrens Hosp Philadelphia Raymond G Perelman Ctr Cellular &

    Mol Therapeut Philadelphia PA;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Childrens Hosp Philadelphia Raymond G Perelman Ctr Cellular &

    Mol Therapeut Philadelphia PA;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

    Univ Toronto Dept Mech &

    Ind Engn Toronto ON M5S 3G8 Canada;

    Hosp Sick Children Program Neurosci &

    Mental Hlth Toronto ON M5G 1X8 Canada;

    Cent S Univ Xiangya Hosp Dept Neurosurg Changsha 410008 Hunan Peoples R China;

    Hosp Sick Children Program Dev &

    Stem Cell Biol Toronto ON M5G 1X8 Canada;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号