Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasion.
Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasion.
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鸟苷酸结合蛋白2调节Drp1介导的线粒体裂变抑制乳腺癌细胞侵袭
DOI：
10.1038/cddis.2017.559
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发表时间：
2017-10-26
影响因子：
9
通讯作者：
Nie C
中科院分区：
文献类型：
--
作者：
Zhang J;Zhang Y;Wu W;Wang F;Liu X;Shui G;Nie C
鸟苷酸结合蛋白2（Guanylate binding protein 2，GBP 2）是γ-干扰素（interferon-γ，IFN-γ）强烈诱导的GT3超家族成员。虽然GBP 2的生化特性已被详细报道，但其生物学功能迄今尚未完全阐明。据我们所知，这项研究首次证明了GBP 2在体外和体内抑制乳腺癌细胞的线粒体分裂和细胞转移。我们以前的工作表明，动力蛋白相关蛋白1（Drp 1）依赖的线粒体分裂在乳腺癌细胞侵袭中起着关键作用。在这项研究中，我们证明GBP 2直接结合到Drp 1。通过shRNA或Mdivi-1（Drp 1特异性抑制剂）消除Drp 1抑制GBP 2的调节功能。此外，GBP 2阻断了Drp 1从胞质到线粒体的易位，从而减弱了Drp 1依赖的线粒体分裂和乳腺癌细胞的侵袭。总之，我们的数据为GBP 2调节乳腺癌细胞侵袭的功能和分子机制提供了新的见解。
Guanylate-binding protein 2 (GBP2) is a member of the large GTPase superfamily that is strongly induced by interferon-γ (IFN-γ). Although the biochemical characteristics of GBP2 have been reported in detail, its biological function has not been thoroughly elucidated to date. To the best of our knowledge, this study presents the first demonstration that GBP2 inhibits mitochondrial fission and cell metastasis in breast cancer cells both in vitro and in vivo. Our previous work demonstrated that dynamin-related protein 1 (Drp1)-dependent mitochondrial fission has a key role in breast cancer cell invasion. In this study, we demonstrate that GBP2 binds directly to Drp1. Elimination of Drp1 by shRNA or Mdivi-1 (a Drp1-specific inhibitor) suppressed GBP2’s regulatory function. Furthermore, GBP2 blocks Drp1 translocation from the cytosol to mitochondria, thereby attenuating Drp1-dependent mitochondrial fission and breast cancer cell invasion. In summary, our data provide new insights into the function and molecular mechanisms underlying GBP2’s regulation of breast cancer cell invasion.
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