ROS up-regulation mediates Ras-induced changes of cell morphology and motility.
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.
Alexandrova
Antonina Y
AY
Institute of Carcinogenesis, Blokhin Memorial Russian Cancer Research Center, Kashirskoye shosse 24, 115478 Moscow, Russia.
Kopnin
Pavel B
PB
Vasiliev
Jury M
JM
Kopnin
Boris P
BP
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D017382:Reactive Oxygen Species; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins