PT  - JOURNAL ARTICLE
AU  - Diaz, Begoña
AU  - Shani, Gidon
AU  - Pass, Ian
AU  - Anderson, Diana
AU  - Quintavalle, Manuela
AU  - Courtneidge, Sara A.
TI  - Tks5-Dependent, Nox-Mediated Generation of Reactive Oxygen Species Is Necessary for Invadopodia Formation
AID  - 10.1126/scisignal.2000368
DP  - 2009 Sep 15
TA  - Science Signaling
PG  - ra53--ra53
VI  - 2
IP  - 88
4099  - http://stke.sciencemag.org/content/2/88/ra53.short
4100  - http://stke.sciencemag.org/content/2/88/ra53.full
SO  - Sci. Signal.2009 Sep 15; 2
AB  - Invadopodia are actin-rich membrane protrusions of cancer cells that facilitate pericellular proteolysis and invasive behavior. We show here that reactive oxygen species (ROS) generated by the NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox) system are necessary for invadopodia formation and function. Knockdown of the invadopodia protein Tks5 [tyrosine kinase substrate with five Src homology 3 (SH3) domains], which is structurally related to the Nox component p47phox, reduces total ROS abundance in cancer cells. Furthermore, Tks5 and p22phox can associate with each other, suggesting that Tks5 is part of the Nox complex. Tyrosine phosphorylation of Tks5 and Tks4, but not other Src substrates, is reduced by Nox inhibition. We propose that Tks5 facilitates the production of ROS necessary for invadopodia formation, and that in turn ROS modulate Tks5 tyrosine phosphorylation in a positive feedback loop.