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 language | English |
|---|---|
| Journal | Science Signaling |
| Volume | 2 |
| Issue number | 88 |
| DOIs | |
| Publication status | Published - Sep 15 2009 |
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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 journal › Article
}
TY - JOUR
T1 - Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary for invadopodia formation
AU - Diaz, Begoña
AU - Shani, Gidon
AU - Pass, Ian
AU - Anderson, Diana
AU - Quintavalle, Manuela
AU - Courtneidge, Sara A.
PY - 2009/9/15
Y1 - 2009/9/15
N2 - 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.
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.
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U2 - 10.1126/scisignal.2000368
DO - 10.1126/scisignal.2000368
M3 - Article
VL - 2
JO - Science Signaling
JF - Science Signaling
SN - 1937-9145
IS - 88
ER -