Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary for invadopodia formation

Begoña Diaz, Gidon Shani, Ian Pass, Diana Anderson, Manuela Quintavalle, Sara A. Courtneidge

Research output: Contribution to journalArticle

145 Citations (Scopus)

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.

Original languageEnglish
JournalScience Signaling
Volume2
Issue number88
DOIs
Publication statusPublished - Sep 15 2009

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Reactive Oxygen Species
Phosphorylation
Tyrosine
Cell Surface Extensions
Cells
Proteolysis
src Homology Domains
Substrates
NADP
Protein-Tyrosine Kinases
Actins
Neoplasms
Oxidoreductases
Membranes
Feedback
Podosomes
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary for invadopodia formation. / Diaz, Begoña; Shani, Gidon; Pass, Ian; Anderson, Diana; Quintavalle, Manuela; Courtneidge, Sara A.

In: Science Signaling, Vol. 2, No. 88, 15.09.2009.

Research output: Contribution to journalArticle

Diaz, Begoña ; Shani, Gidon ; Pass, Ian ; Anderson, Diana ; Quintavalle, Manuela ; Courtneidge, Sara A. / Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary for invadopodia formation. In: Science Signaling. 2009 ; Vol. 2, No. 88.
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