Mitochondrial dysfunction and reactive oxygen species imbalance promote breast cancer cell motility through a CXCL14-mediated mechanism.
Mitochondrial dysfunction and reactive oxygen species imbalance promote breast cancer cell motility through a CXCL14-mediated mechanism.
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DOI：
10.1158/0008-5472.can-08-3359
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发表时间：
2009-03-15
期刊：
影响因子：
11.2
通讯作者：
Huang P
中科院分区：
文献类型：
--
作者：
Pelicano H;Lu W;Zhou Y;Zhang W;Chen Z;Hu Y;Huang P
虽然线粒体功能障碍和活性氧（ROS）的压力已经在癌细胞中观察到很长时间，它们在促进恶性细胞行为的作用仍然不清楚。在这里，我们表明，在乳腺癌细胞中的线粒体呼吸链的扰动导致产生的细胞亚克隆增加的ROS，活跃的增殖，高细胞运动性，并在体外和体内的侵入行为。使用微阵列的基因表达分析显示，所有的亚克隆过表达CXCL 14，一种功能不明的新型趋化因子。我们进一步表明，CXCL 14的表达上调活性氧通过激活蛋白-1信号通路，并促进细胞运动，通过结合到内质网上的肌醇1，4，5-三磷酸受体的胞浆Ca 2+的升高。使用诱饵方法消除CXCL 14表达抑制细胞运动性和侵袭。我们的数据表明，线粒体功能障碍和ROS应激通过CXCL 14介导的新途径促进癌细胞运动。
Although mitochondrial dysfunction and reactive oxygen species (ROS) stress have long been observed in cancer cells, their role in promoting malignant cell behavior remains unclear. Here, we show that perturbation of the mitochondrial respiratory chain in breast cancer cells leads to a generation of subclones of cells with increased ROS, active proliferation, high cellular motility, and invasive behaviors in vitro and in vivo. Gene expression analysis using microarrays revealed that all subclones overexpressed CXCL14, a novel chemokine with undefined function. We further show that CXCL14 expression is up-regulated by ROS through the activator protein-1 signaling pathway and promotes cell motility through elevation of cytosolic Ca2+ by binding to the inositol 1,4,5-trisphosphate receptor on the endoplasmic reticulum. Abrogation of CXCL14 expression using a decoy approach suppressed cell motility and invasion. Our data suggest that mitochondrial dysfunction and ROS stress promote cancer cell motility through a novel pathway mediated by CXCL14.