Hypoxia-induced reactive oxygen species mediate N-cadherin and SERPINE1 expression, EGFR signalling and motility in MDA-MB-468 breast cancer cells.
Hypoxia-induced reactive oxygen species mediate N-cadherin and SERPINE1 expression, EGFR signalling and motility in MDA-MB-468 breast cancer cells.
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DOI：
10.1038/s41598-017-15474-7
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发表时间：
2017-11-09
影响因子：
4.6
通讯作者：
Monteith GR
中科院分区：
文献类型：
--
作者：
Azimi I;Petersen RM;Thompson EW;Roberts-Thomson SJ;Monteith GR
肿瘤微环境的特征之一是由于增殖性癌细胞耗氧量增加和血管系统改变而导致的缺氧。低氧张力启动各种细胞信号，并可驱动上皮细胞向间充质细胞的转变(EMT)，这是癌症进展中的一个重要过程。在这项研究中，我们利用抗氧化剂N-乙酰半胱氨酸(NAC)，我们证明了低氧诱导的MDA-MB-468乳腺癌细胞中的ROS，选择性地调节低氧诱导的N-钙粘蛋白和SERPINE1的增加，这两个蛋白质与细胞黏附有关。NAC处理细胞也可减弱低氧诱导的表皮生长因子受体的激活，但对低氧诱导的HIF1α无任何影响。外源性过氧化氢在低氧条件下对N-钙粘蛋白和SERPINE1的表达及EGFR的激活有明显影响，提示其可能参与了低氧介导的这些事件。反映了它们对细胞黏附蛋白和EGFR(与迁移表型相关)的影响，NAC还减少了低氧条件下的细胞迁移，这是转移中的关键事件。我们的发现表明，氧化还原信号在调节乳腺癌细胞对低氧和EMT反应的特定成分中具有选择性作用。这项研究为靶向ROS作为控制乳腺癌转移的治疗策略的潜力提供了新的证据。
One of the hallmarks of the tumour microenvironment is hypoxia resulting from increased oxygen consumption by proliferative cancer cells and altered vasculature. Hypoxic tension initiates various cellular signals and can drive epithelial to mesenchymal transition (EMT), a process important in cancer progression. In this study, using the antioxidant N-acetylcysteine (NAC), we show that hypoxia-induced reactive oxygen species (ROS) in MDA-MB-468 breast cancer cells, selectively regulate hypoxia-induced increases in N-cadherin and SERPINE1, two proteins involved in cell adhesion. Treatment of cells with NAC also attenuated hypoxia-mediated activation of EGFR, but did not have any effect on hypoxia-mediated induction of HIF1α. Exogenous hydrogen peroxide phenocopied the effects of hypoxia on N-cadherin and SERPINE1 expression and EGFR activation, suggesting its possible involvement in these hypoxia-mediated events. Reflective of their effect on cell adhesion proteins and EGFR (associated with migratory phenotypes), NAC also reduced cell migration under hypoxic conditions, a crucial event in metastasis. Our findings suggest a selective role for redox signalling in the regulation of specific components of the responses to hypoxia and induction of EMT in breast cancer cells. This study provides new evidence supporting the potential of targeting ROS as a therapeutic strategy for the control of breast cancer metastasis.
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影响因子：
9
作者：
通讯作者：
--
钙和ROS：相互互动。
影响因子：
11.4
作者：
Görlach A;Bertram K;Hudecova S;Krizanova O
通讯作者：
Krizanova O
影响因子：
--
作者：
Evensen NA;Li Y;Kuscu C;Liu J;Cathcart J;Banach A;Zhang Q;Li E;Joshi S;Yang J;Denoya PI;Pastorekova S;Zucker S;Shroyer KR;Cao J
通讯作者：
Cao J
DOI：
10.1152/ajpregu.00636.2002
发表时间：
2003-10-01
影响因子：
2.8
作者：
Chen, YF;Cowley, AW;Zou, AP
通讯作者：
Zou, AP
影响因子：
--
作者：
Czekay RP;Wilkins-Port CE;Higgins SP;Freytag J;Overstreet JM;Klein RM;Higgins CE;Samarakoon R;Higgins PJ
通讯作者：
Higgins PJ