增强的线粒体分裂通过一种依赖活性氧的机制抑制三阴性乳腺癌细胞迁移。
Enhanced mitochondrial fission inhibits triple-negative breast cancer cell migration through an ROS-dependent mechanism.
作者信息
Humphries Brock A, Zhang Anne, Buschhaus Johanna M, Bevoor Avinash, Farfel Alex, Rajendran Shrila, Cutter Alyssa C, Luker Gary D
机构信息
Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
iScience. 2023 May 3;26(6):106788. doi: 10.1016/j.isci.2023.106788. eCollection 2023 Jun 16.
Mitochondria produce reactive oxygen species (ROS), which function in signal transduction. Mitochondrial dynamics, encompassing morphological shifts between fission and fusion, can directly impact ROS levels in cancer cells. In this study, we identified an ROS-dependent mechanism for how enhanced mitochondrial fission inhibits triple negative breast cancer (TNBC) cell migration. We found that enforcing mitochondrial fission in TNBC resulted in an increase in intracellular ROS levels and reduced cell migration and the formation of actin-rich migratory structures. Consistent with mitochondrial fission, increasing ROS levels in cells inhibited cell migration. Conversely, reducing ROS levels with either a global or mitochondrially targeted scavenger overcame the inhibitory effects of mitochondrial fission. Mechanistically, we found that the ROS sensitive SHP-1/2 phosphatases partially regulate inhibitory effects of mitochondrial fission on TNBC migration. Overall, our work reveals the inhibitory effects of ROS in TNBC and supports mitochondrial dynamics as a potential therapeutic target for cancer.
线粒体产生活性氧（ROS），其在信号转导中发挥作用。线粒体动力学，包括裂变和融合之间的形态变化，可直接影响癌细胞中的ROS水平。在本研究中，我们确定了一种ROS依赖性机制，即增强的线粒体裂变如何抑制三阴性乳腺癌（TNBC）细胞迁移。我们发现，在TNBC中强制线粒体裂变会导致细胞内ROS水平升高，并减少细胞迁移以及富含肌动蛋白的迁移结构的形成。与线粒体裂变一致，细胞内ROS水平升高会抑制细胞迁移。相反，使用全身性或线粒体靶向清除剂降低ROS水平可克服线粒体裂变的抑制作用。从机制上讲，我们发现ROS敏感的SHP-1/2磷酸酶部分调节线粒体裂变对TNBC迁移的抑制作用。总体而言，我们的工作揭示了ROS在TNBC中的抑制作用，并支持线粒体动力学作为癌症的潜在治疗靶点。
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