Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen.
Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen.
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DOI：
10.1038/s41467-018-06988-3
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发表时间：
2018-10-31
影响因子：
16.6
通讯作者：
Mikaelian I
中科院分区：
文献类型：
--
作者：
Deygas M;Gadet R;Gillet G;Rimokh R;Gonzalo P;Mikaelian I
130年前，细菌对氧的趋氧性或趋化性被描述。在真核生物中，目前描述的对缺氧的主要适应依赖于HIF转录因子。为了研究高等真核生物的趋氧性是否是保守的，开发了一种基于细胞禁闭后缺氧自生成的方法。我们发现，上皮细胞从各种组织迁移的极端方向性向氧气逃避缺氧，独立的HIF途径。我们提供的证据表明，伴随着氧气梯度，活性氧（ROS）的梯度下发展限制和抗氧化剂抑制趋氧性。最后，我们确定，在乳腺细胞中，EGF受体，其活性增强的ROS和缺氧抑制，代表的分子靶点，指导缺氧细胞的氧气。我们的研究结果表明，趋氧性是高等真核细胞的一种属性，并从氧转化为ROS的收益。趋氧性，即对氧气的趋化性，发生在细菌中，也可能发生在癌细胞中。在这里，作者发现来自不同组织的受限细胞通过趋氧性逃避缺氧，这是一个独立于线粒体和HIF途径的过程，并且依赖于乳腺细胞中ROS梯度的EGF受体解释。
Aerotaxis or chemotaxis to oxygen was described in bacteria 130 years ago. In eukaryotes, the main adaptation to hypoxia currently described relies on HIF transcription factors. To investigate whether aerotaxis is conserved in higher eukaryotes, an approach based on the self-generation of hypoxia after cell confinement was developed. We show that epithelial cells from various tissues migrate with an extreme directionality towards oxygen to escape hypoxia, independently of the HIF pathway. We provide evidence that, concomitant to the oxygen gradient, a gradient of reactive oxygen species (ROS) develops under confinement and that antioxidants dampen aerotaxis. Finally, we establish that in mammary cells, EGF receptor, the activity of which is potentiated by ROS and inhibited by hypoxia, represents the molecular target that guides hypoxic cells to oxygen. Our results reveals that aerotaxis is a property of higher eukaryotic cells and proceeds from the conversion of oxygen into ROS. Aerotaxis, chemotaxis towards oxygen, occurs in bacteria and likely in cancer cells. Here the authors find that confined cells from different tissues escape hypoxia by aerotaxis, a process independent of mitochondria and the HIF pathway, and dependent on EGF receptor interpretation of a ROS gradient in mammary cells.
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影响因子：
13.3
作者：
Chen, Yongqiang;Henson, Elizabeth S.;Gibson, Spencer B.
通讯作者：
Gibson, Spencer B.
影响因子：
16.6
作者：
Ermakova YG;Bilan DS;Matlashov ME;Mishina NM;Markvicheva KN;Subach OM;Subach FV;Bogeski I;Hoth M;Enikolopov G;Belousov VV
通讯作者：
Belousov VV
影响因子：
15.8
作者：
Greulich H;Chen TH;Feng W;Jänne PA;Alvarez JV;Zappaterra M;Bulmer SE;Frank DA;Hahn WC;Sellers WR;Meyerson M
通讯作者：
Meyerson M
影响因子：
14.8
作者：
Paulsen, Candice E.;Truong, Thu H.;Garcia, Francisco J.;Homann, Arne;Gupta, Vinayak;Leonard, Stephen E.;Carroll, Kate S.
通讯作者：
Carroll, Kate S.
影响因子：
56.9
作者：
Genbacev, O;Zhou, Y;Fisher, SJ
通讯作者：
Fisher, SJ