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Updated: Feb 27, 2026
Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
Published on: August 27, 2012
Differential Depth Sensing Reduces Cancer Cell Proliferation via Rho-Rac-Regulated Invadopodia
Parthiv Kant Chaudhuri1, Catherine Qiurong Pan1, Boon Chuan Low1,2,3
1Mechanobiology Institute, National University of Singapore , 5A Engineering Drive 1, Singapore 117411, Singapore.
Abstract:
Bone, which is composed of a porous matrix, is one of the principal secondary locations for cancer. However, little is known about the effect of this porous microenvironment in regulating cancer cell proliferation. Here, we examine how the depth of the pores can transduce a mechanical signal and reduce the proliferation of noncancer breast epithelial cells (MCF-10A) and malignant breast cancer cells (MDA-MB-231 and MCF-7) using micrometer-scale topographic features. Interestingly, cells extend actin-rich protrusions, such as invadopodia, to sense the depth of the matrix pore and activate actomyosin contractility to decrease MCF-10A proliferation. However, in MDA-MB-231, depth sensing inactivates Rho-Rac-regulated actomyosin contractility and phospho-ERK signaling. Inhibiting contractility on this porous matrix using blebbistatin further reduces MDA-MB-231 proliferation. Our findings support the notion of mechanically induced dormancy through depth sensing, where invadopodia-mediated depth sensing can inhibit the proliferation of noncancer and malignant breast cancer cells through differential regulation of actomyosin contractility.
Insights
Cancer cells in bone
Area of Science:
- Biomedical Engineering
- Cell Biology
- Cancer Research
Background:
- Bone is a common site for cancer metastasis.
- The role of the bone's porous microenvironment in regulating cancer cell proliferation is not well understood.
Purpose of the Study:
- To investigate how pore depth in a bone-like matrix mechanically influences cancer cell proliferation.
- To explore the cellular mechanisms, including invadopodia and actomyosin contractility, involved in this process.
Main Methods:
- Utilized micrometer-scale topographic features to mimic bone porosity.
- Examined noncancerous (MCF-10A) and cancerous (MDA-MB-231, MCF-7) breast cells.
- Assessed cell proliferation, invadopodia formation, and actomyosin contractility.
- Used blebbistatin to inhibit contractility.
Main Results:
- Pore depth acts as a mechanical signal regulating cell proliferation.
- Invadopodia-mediated depth sensing activates actomyosin contractility in noncancer cells, reducing proliferation.
- In malignant cells, depth sensing inactivates contractility and phospho-ERK signaling, with blebbistatin further decreasing proliferation.
Conclusions:
- Mechanically induced dormancy occurs via depth sensing in a porous microenvironment.
- Invadopodia-mediated depth sensing differentially regulates actomyosin contractility to inhibit proliferation in both normal and malignant breast cells.
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