Abstract
Transformation by the ras oncogene can result in promotion of metastasis as well as induction of senescence via increased tissue remodeling, for example, by matrix metalloproteases. Increased production of mitochondrial reactive oxygen species (mtROS) via NADPH oxidase 4 (NOX4) is implicated in this process. Hydrogen peroxide-inducible clone-5 (HIC-5) is postulated to sense both matrix detachment of transformed cells and intracellular ROS and can inhibit ras signaling via inhibition of NOX4.