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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts

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Transducer of Cdc42-dependent actin assembly promotes epidermal growth factor-induced cell motility and invasiveness

Jinghui Hu1, Alka Mukhopadhyay, Andrew W B Craig

  • 1Department of Biochemistry and the Cancer Biology and Genetics Division, Queen's University Cancer Research Institute, Queen's University Kingston, Ontario K7L 3N6, Canada.

The Journal of Biological Chemistry
|November 11, 2010
PubMed

Insights

Toca-1 (transducer of Cdc42-dependent actin assembly) is crucial for coordinating actin assembly in cell structures like lamellipodia. Its deficiency impairs EGF-induced cell migration and invasion.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Toca-1 (transducer of Cdc42-dependent actin assembly) is known to interact with actin assembly pathways.
  • Its specific role in lamellipodia formation and cell motility remained uninvestigated.

Purpose of the Study:

  • To investigate the role of Toca-1 in epidermal growth factor (EGF)-induced cell protrusions, migration, and invasion.

Main Methods:

  • Utilized RNA interference for stable knockdown of Toca-1 expression in A431 cells.
  • Observed Toca-1 localization, co-localization with F-actin and Arp2/3 complex, and tyrosine phosphorylation upon EGF stimulation.
  • Assessed EGF-induced filopodia, lamellipodial protrusions, motility, and invasiveness in Toca-1 knockdown cells.

Main Results:

  • EGF induces Toca-1 localization to lamellipodia, co-localizing with F-actin and Arp2/3 complex.
  • EGF stimulation leads to tyrosine phosphorylation and interaction of Toca-1 with N-WASP and Abi1.
  • Toca-1 knockdown cells exhibit defects in EGF-induced filopodia, lamellipodial protrusions, motility, and invasiveness, with impaired Arp2/3 and Abi1 localization.

Conclusions:

  • Toca-1 plays a significant role in coordinating actin assembly within filopodia and lamellipodia.
  • Toca-1 is essential for promoting EGF-induced cell migration and invasion by regulating actin dynamics.

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