• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Rapid activation of FAK/mTOR/p70S6K/PAK1-signaling controls the early testosterone-induced actin reorganization in colon cancer cells
【24h】

Rapid activation of FAK/mTOR/p70S6K/PAK1-signaling controls the early testosterone-induced actin reorganization in colon cancer cells

机译：FAK / mTOR / p70S6K / PAK1信号的快速激活控制结肠癌细胞中早期睾丸激素诱导的肌动蛋白重组

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

Actin cytoskeleton reorganization initiated by testosterone conjugates through activation of membrane androgen receptors (mAR) has recently been reported in colon tumor cells. This mAR-induced actin reorganization was recognized as a critical initial event, controlling apoptosis and inhibiting cell migration. The present study addressed the molecular signaling regulating the rapid actin remodeling initiated upon testosterone-induced mAR activation in Caco2 colon tumor cells. We report early phosphorylation of the Focal Adhesion Kinase (FAK), followed by substantial early phosphorylation of mammalian target of rapamycin (mTOR), S6 kinase (p70S6K) and the actin regulating p21-activated kinase (PAK1). Pharmacological inhibition of FAK-sensitive phosphatidylinositide-3-kinase (PI-3K), a known element of mAR-signaling, fully abrogated the testosterone-induced actin reorganization and the activation of mTOR, p70S6K and PAK1. Similarly, inhibition of mTOR blocked p70S6K and PAK1 phosphorylation and actin remodeling. Pretreatment of the cells with the intracellular androgen receptor (iAR) antagonist flutamide or silencing iAR through siRNA did not influence mTOR phosphorylation and actin reorganization, indicating specific mAR-induced testosterone effects that are independent of iAR signaling. In conclusion, we demonstrate for the first time a new mAR-governed pathway involving FAK/PI-3K and mTOR/p70S6K/PAK1-cascade that regulates early actin reorganization in colon cancer cells.
机译：最近报道了结肠肿瘤细胞中由睾丸激素结合物通过激活膜雄激素受体（mAR）引发的肌动蛋白细胞骨架重组。这种mAR诱导的肌动蛋白重组被认为是关键的初始事件，控制细胞凋亡并抑制细胞迁移。本研究解决了在睾丸激素诱导的Caco2结肠肿瘤细胞中mAR活化后启动的快速肌动蛋白重塑的分子信号传导。我们报告了局灶性粘附激酶（FAK）的早期磷酸化，随后是哺乳动物雷帕霉素（mTOR），S6激酶（p70S6K）和肌动蛋白调节p21活化激酶（PAK1）的靶点的实质早期磷酸化。 FAR敏感的磷脂酰肌醇3激酶（PI-3K）（mAR信号的已知成分）的药理抑制作用完全消除了睾丸激素诱导的肌动蛋白重组以及mTOR，p70S6K和PAK1的激活。同样，抑制mTOR会阻断p70S6K和PAK1磷酸化和肌动蛋白重塑。用细胞内雄激素受体（iAR）拮抗剂氟他胺或通过siRNA沉默iAR进行细胞预处理不会影响mTOR磷酸化和肌动蛋白重组，这表明mAR诱导的特定睾丸激素效应与iAR信号传导无关。总之，我们首次证明了一种新的由mAR调控的途径，涉及FAK / PI-3K和mTOR / p70S6K / PAK1级联，可调节结肠癌细胞中的早期肌动蛋白重组。

著录项

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