Molecular and Cellular Biochemistry

, Volume 340, Issue 1–2, pp 195–202

ROS-NFκΒ mediates TGF-β1-induced expression of urokinase-type plasminogen activator, matrix metalloproteinase-9 and cell invasion

  • Nicolas Tobar
  • Victor Villar
  • Juan F. Santibanez
Article

Abstract

TGF-β1 has been postulated as a pro-oncogenic factor in the late step of the tumoral progression. In transformed cells, TGF-β1 enhances the capacity to degrade the extracellular matrix, cell invasiveness and epithelial-mesenchymal transition, which are crucial steps for metastasis. Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) are critical components in cell migration and invasion induced by TGF-β1, however, the exact mechanism by which TGF-β1 regulates uPA and MMP-9 is not well elucidated so far. In the present study, we analyzed the role of ROS-NFκΒ, signal as mediator in the cell malignity enhancement by TGF-β1. We found that TGF-β1 activates NFκΒ, through Rac1-NOXs-ROS-dependent mechanism. Our results shows that TGF-β1 stimulation of uPA and MMP-9 expression involve NOXs-dependent ROS and NFκΒ, activation, demonstrated by using DPI, NOXs inhibitor, ROS scavenger N-acetylcysteine and SN50, an NFkb inhibitor. Furthermore, we found that the inhibition of ROS and NFκΒ, abrogates TGF-β1 stimulation of EMT, cell motility and invasion. Thus, ROS-NFκΒ acts as the crucial signal in TGF-β1-induced uPA and MMP-9 expression thereby mediating the enhancement of cellular malignity by TGF-β1.

Keywords

TGF-β NFκΒ uPA MMP-9 EMT Migration Invasion 

Abbreviations

TGF-β1

Transforming growth factor-β1

NFκΒ

Nuclear factor κ beta

ROS

Reactive oxygen species

NOX

NADPH oxidase

uPA

Urokinase type plasminogen activator

MMP-9

Matrix metalloproteinase-9

EMT

Epithelial-mesenchymal transition

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Nicolas Tobar
    • 1
  • Victor Villar
    • 1
  • Juan F. Santibanez
    • 1
    • 2
  1. 1.Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, (INTA)Universidad de ChileSantiagoChile
  2. 2.Laboratory of Experimental Hematology, Institute for Medical Research (IMI)University of BelgradeBelgradeSerbia

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