Reactive Oxygen Generated by NADPH Oxidase 1 (Nox1) Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration Reactive oxygen generated by NADPH oxidase 1 (Nox1) contributes to cell invasion by regulating matrix metalloprotease-9 production and cell migration
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This research was originally published in J. Biol. Chem. Masahiro Shinohara, Yoshifumi Adachi, Junji Mitsushita, Mitsuhiro Kuwabara, Atsushi Nagasawa, Saori Harada, Shuichi Furuta, Yugen Zhang, Kajla Seheli, Hitoshi Miyazaki and Tohru Kamata. Enhancement of Reactive Oxygen Species Production and Chlamydial Infection by the Mitochondrial Nod-like Family Member NLRX1 . J. Biol. Chem. 2010 285: 41637-41645. Copyright (c) the American Society for Biochemistry and Molecular BiologyA mediating role of the reactive oxygen species-generating enzyme Nox1 has been suggested for Ras oncogene transformation phenotypes including anchorage-independent cell growth, augmented angiogenesis, and tumorigenesis. However, little is known about whether Nox1 signaling regulates cell invasiveness. Here, we report that the cell invasion activity was augmented in K-Ras-transformed normal rat kidney cells and attenuated by transfection of Nox1 small interference RNAs(siRNAs) into the cells. Diphenyleneiodonium (DPI) or Nox1 siRNAs blocked up-regulation of matrix metalloprotease-9 at both protein and mRNA levels in K-Ras-transformed normal rat kidney cells. Furthermore, DPI and Nox1 siRNAs inhibited the activation of IKK alpha kinase and the degradation of I kappa B alpha, suppressing the NF kappa B-dependent matrix metalloprotease-9 promoter activity. Additionally, epidermal growth factor-stimulated migration of CaCO-2 cells was abolished by DPI and Nox1 siRNAs, indicating the requirement of Nox1 activity for the motogenic effect of epidermal growth factor. This Nox1 action was mediated by down-regulation of the Rho activity through the low molecular weight protein-tyrosine phosphatase-p190RhoGAP-dependent mechanism. Taken together, our findings define a mediating role of Nox1-generated reactive oxygen species in cell invasion processes, most notably metalloprotease production and cell motile activity.
- JOURNAL OF BIOLOGICAL CHEMISTRY
JOURNAL OF BIOLOGICAL CHEMISTRY 285(7), 4481-4488, 2010-02-12
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC