English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/32362
Title: Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability
Authors: Radisky, Derek C.; Levy, Dinah D.; Littlepage, Laurie E.; Liu, Hong; Nelson, Celeste M.; Fata, Jimmie E.; Leake, Devin; Godden, Elizabeth L.; Albertson, Donna G.; Nieto, M. Ángela; Werb, Zena; Bissell, Mina J.
Issue Date: 7-Jul-2005
Publisher: Nature Publishing Group
Citation: Nature 436: 123-127 (2006)
Abstract: The tumour microenvironment can be a potent carcinogen, not only by facilitating cancer progression and activating dormant cancer cells, but also by stimulating tumour formation1. We have previously investigated stromelysin-1/matrix metalloproteinase-3 (MMP-3), a stromal enzyme upregulated in many breast tumours2, and found that MMP-3 can cause epithelial–mesenchymal transition (EMT) and malignant transformation in cultured cells3, 4, 5, and genomically unstable mammary carcinomas in transgenic mice3. Here we explain the molecular pathways by which MMP-3 exerts these effects: exposure of mouse mammary epithelial cells to MMP-3 induces the expression of an alternatively spliced form of Rac1, which causes an increase in cellular reactive oxygen species (ROS). The ROS stimulate the expression of the transcription factor Snail and EMT, and cause oxidative damage to DNA and genomic instability. These findings identify a previously undescribed pathway in which a component of the breast tumour microenvironment alters cellular structure in culture and tissue structure in vivo, leading to malignant transformation.
Description: 5 páginas, 4 figuras.-- Letter.
Publisher version (URL): http://dx.doi.org/10.1038/nature03688
URI: http://hdl.handle.net/10261/32362
DOI: 10.1038/nature03688
ISSN: 0028-0836
Appears in Collections:(IN) Artículos
Files in This Item:
There are no files associated with this item.
Show full item record

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.