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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
Published on: August 27, 2012
Adhesion rings surround invadopodia and promote maturation
Kevin M Branch1, Daisuke Hoshino, Alissa M Weaver
1Department of Cancer Biology, Vanderbilt University School of Medicine , Nashville, TN 37232 , USA.
Biology Open
|December 6, 2012
Summary
Adhesion rings form around invadopodia, crucial for cancer cell invasion. Inhibiting integrins or ILK disrupts these rings, reducing matrix degradation and proteinase secretion, revealing a new regulatory mechanism.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Cancer cell invasion and metastasis involve extracellular matrix (ECM) degradation.
- Invadopodia are actin-rich structures responsible for focal ECM degradation via secreted proteinases.
- The role of adhesion signaling in invadopodia regulation is not well understood.
Purpose of the Study:
- To investigate the role of adhesion signaling in invadopodia formation and function.
- To determine the relationship between adhesion structures and invadopodium activity.
- To elucidate the mechanism by which adhesion influences ECM degradation.
Main Methods:
- Live cell imaging to observe invadopodia dynamics and adhesion ring formation.
- Inhibition of RGD-binding integrins and knockdown of integrin-linked kinase (ILK).
- Assessment of ECM degradation, IQGAP recruitment, and MT1-MMP accumulation at invadopodia.
Main Results:
- Adhesion rings form around invadopodia and correlate with their activity.
- Inhibition of integrins or ILK reduced invadopodia number, ECM degradation, and MT1-MMP recruitment.
- MT1-MMP knockdown affected invadopodia activity but not adhesion ring formation.
Conclusions:
- Adhesion rings promote invadopodium maturation by enhancing proteinase secretion.
- Adhesion rings are critical regulators of invadopodia-mediated ECM degradation.
- Invadopodia share similarities with podosomes, structures found in normal cells.
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