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Related Experiment Video

Updated: May 27, 2026

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

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

Published on: August 27, 2012

Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway.

Marco A O Magalhaes¹, Daniel R Larson, Christopher C Mader

¹Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA.

The Journal of Cell Biology

|November 23, 2011

Summary

Tumor cell invasion relies on invadopodia dynamics. This study reveals how pH changes, regulated by NHE1 and cortactin, control cofilin release, essential for invadopodia function and cancer cell invasion.

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Area of Science:

Cell Biology
Cancer Research
Biochemistry

Background:

Invadopodia are crucial for tumor cell invasion and proteolytic activity.
Cortactin phosphorylation is vital for invadopodia maturation, influencing Nck1 and cofilin.
The exact mechanism of cortactin-cofilin regulation in invadopodia remains unclear.

Purpose of the Study:

To elucidate the role of local pH in cortactin-cofilin interactions at invadopodia.
To investigate the mechanism of cortactin-mediated regulation of cofilin activity.
To understand the contribution of this pathway to invadopodia dynamics and cancer cell invasion.

Main Methods:

Investigated cortactin-cofilin binding under varying pH conditions.
Utilized biochemical assays to assess NHE1 recruitment and activity.
Observed invadopodia protrusion/retraction dynamics in 3D cell culture models.

Main Results:

Cortactin-cofilin binding is modulated by local pH changes at invadopodia, mediated by NHE1.
Cortactin tyrosine phosphorylation recruits NHE1, increasing local pH and releasing cofilin.
This pH-dependent mechanism regulates invadopodia dynamics and is critical for 3D cell invasion.

Conclusions:

Identified a novel pH-dependent regulatory pathway for invadopodia function.
Demonstrated that cortactin phosphorylation, local pH increase, and cofilin activation are essential for cancer cell invasion.
This pathway represents a potential target for anti-invasion therapies.