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Reactive oxygen species (ROS) are increasingly recognized as important signaling regulators. The family of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox's) is responsible for the production of most signaling ROS in cells. An emerging paradigm is that individual Nox family members are organized and activated at distinct subcellular locations for specific functions. Tyrosine kinase substrate (Tks) family adaptor proteins have now been identified as Nox organizer proteins that enhance the production of ROS at invadopodia and podosomes, which are subcellular adhesion structures associated with extracellular matrix degradation. ROS production is also shown to be required for invadopodia and podosome formation. These findings broaden the known signaling roles of ROS and identify a potential mechanism for the correlation of ROS production with cancer invasion.