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

Sci. Signal., 15 September 2009
Vol. 2, Issue 88, p. ra53
DOI: 10.1126/scisignal.2000368

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

  1. Begoña Diaz*,
  2. Gidon Shani*,
  3. Ian Pass,
  4. Diana Anderson,
  5. Manuela Quintavalle, and
  6. Sara A. Courtneidge
  1. Tumor Microenvironment Program, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  1. To whom correspondence should be addressed. E-mail: courtneidge{at}burnham.org
  • * The order of these authors was chosen by lot.

Abstract

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.

Citation:

B. Diaz, G. Shani, I. Pass, D. Anderson, M. Quintavalle, and S. A. Courtneidge, Tks5-Dependent, Nox-Mediated Generation of Reactive Oxygen Species Is Necessary for Invadopodia Formation. Sci. Signal. 2, ra53 (2009).

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