TITLE

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

AUTHOR(S)
Tobar, Nicolas; Villar, Victor; Santibanez, Juan F.
PUB. DATE
July 2010
SOURCE
Molecular & Cellular Biochemistry;Jul2010, Vol. 340 Issue 1/2, p195
SOURCE TYPE
Academic Journal
DOC. TYPE
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.
ACCESSION #
51397718

 

Related Articles

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics