Center for Core Facility and Advanced Technologies, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Department of Oncology, Guizhou People's Hospital, Guizhou 550002, China.
Cell Death Dis. 2017 Oct 26;8(10):e3151. doi: 10.1038/cddis.2017.559.
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.
鸟苷酸结合蛋白 2（GBP2）是一种大 GTPase 超家族的成员，其强烈受到干扰素-γ（IFN-γ）的诱导。尽管 GBP2 的生化特性已被详细报道，但截至目前，其生物学功能尚未被彻底阐明。据我们所知，本研究首次证明 GBP2 在体外和体内均抑制乳腺癌细胞中的线粒体裂变和细胞转移。我们之前的工作表明，依赖于动力相关蛋白 1（Drp1）的线粒体裂变在乳腺癌细胞侵袭中起关键作用。在本研究中，我们证明 GBP2 可直接与 Drp1 结合。通过 shRNA 或 Mdivi-1（Drp1 特异性抑制剂）消除 Drp1 可抑制 GBP2 的调节功能。此外，GBP2 阻止 Drp1 从细胞质向线粒体易位，从而减弱 Drp1 依赖性线粒体裂变和乳腺癌细胞侵袭。总之，我们的数据为 GBP2 调节乳腺癌细胞侵袭的功能和分子机制提供了新的见解。
