ROS up-regulatlion mediates Ras-induced changes of cell morphology and motility

被引:67
作者
Alexandrova, Antonina Y.
Kopnin, Pauel B.
Vasiliev, Jury M.
Kopnin, Boris P.
机构
[1] Blokhin Mem Russian Canc Res Ctr, Inst Carcinogenesis, Moscow 115478, Russia
[2] Engelhardt Inst Mol Biol, Moscow, Russia
[3] Univ Oslo, Moscow Ctr Med Res, Moscow, Russia
基金
俄罗斯基础研究基金会;
关键词
ROS; Ras oncogene; Rho GTPases; cell morphology; motility;
D O I
10.1016/j.yexcr.2006.03.004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Expression of activated Ras causes an increase in intracellular content of reactive oxygen species (ROS). To determine the role of ROS up-regulation in mediation of Ras-induced morphological transformation and increased cell motility, we studied the effects of hydrogen peroxide and antioxidant NAC on morphology of REF52 rat fibroblasts and their ability to migrate into the wound in vitro. Treatment with low dosages of hydrogen peroxide leading to 1.5- to 2-fold increase in intracellular ROS levels induced changes of cell shape, actin cytoskeleton organization, cell adhesions and migration resembling those in Ras-transformed cells. On the other hand, treatment with NAC attenuating ROS up-regulation in cells with conditional or constitutive expression of activated Ras led to partial reversion of morphological transformation and decreased cell motility. The effect of ROS on cell morphology and motility probably results from modulation of activity of Rac1, Rho, and cofilin proteins playing a key role in regulation of actin dynamics. The obtained data are consistent with the idea that ROS up-regulation mediates two key events in Ras-induced morphological transformation and cell motility: it is responsible for Rac1 activation and is necessary (though insufficient) for realization of Ras-induced cofilin dephosphorylation. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:2066 / 2073
页数:8
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