Matrix metalloproteases (MMPs) create havoc both outside and inside a cell to pave the way for tumorigenesis, based on findings from Derek Radisky, Mina Bissell (Berkeley Lab, Berkeley, CA), and colleagues.
MMPs are known to support cancer progression by their ability to degrade the matrix and clear the way for invasion and metastasis. Bissell's lab now shows that MMP-3 can also stimulate genomic instability, a key tumor characteristic, in mammary epithelial cells.
The genomic instability stems from mitochondrial production of the reactive oxygen species (ROS) superoxide, which altered the genotype and phenotype of mammary epithelial cells. The authors show that ROS are sufficient to reproduce the effects of MMP treatment, and that quenching ROS prevents MMP-3–induced genomic rearrangements and cell motility. The authors are now investigating the link between ROS and motility.
Superoxide is made in response to the induction of an overactive splice variant...
