Research ArticleCancer

Tks5-Dependent, Nox-Mediated Generation of Reactive Oxygen Species Is Necessary for Invadopodia Formation

Science Signaling  15 Sep 2009:
Vol. 2, Issue 88, pp. ra53
DOI: 10.1126/scisignal.2000368

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Signals to Invade

Cancer is characterized by the invasion of surrounding healthy tissues, a process that is facilitated by invadopodia, actin-rich membrane protrusions thought to coordinate cell attachment to the extracellular matrix with its degradation. Indeed, the presence of invadopodia on cancer cells correlates with their invasiveness. Cancer cell invasion and metastasis has also been associated with the production of reactive oxygen species (ROS) and, here, Diaz et al. implicate localized production of ROS by the NADPH oxidase (Nox) complex in invadopodia formation and function. They showed that Tks5, a scaffolding protein found in invadopodia, was crucial to ROS production in cancer cells, likely through an association with the Nox component p22phox. Moreover, Tks5 phosphorylation, which is required for the formation of functional invadopodia, depended on ROS production, suggesting the existence of a positive feedback loop in which Tks5 promotes ROS formation and thereby its own phosphorylation.

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