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MMP proteolytic activity regulates cancer invasiveness by modulating integrins
Alakesh Das1, Melissa Monteiro1, Amlan Barai1
1Department of Biosciences & Bioengineering, IIT Bombay, Mumbai, 400 076, India.
Scientific Reports
|October 29, 2017
Summary
Matrix metalloproteinases (MMPs) enable cancer cell invasion by degrading the extracellular matrix (ECM). MMP activity regulates cancer cell biophysical properties like spreading and stiffness, crucial for migration.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Cancer cell invasion relies on matrix metalloproteinases (MMPs) to degrade the extracellular matrix (ECM).
- The precise impact of ECM degradation by MMPs on cancer cell biophysical characteristics remains incompletely understood.
- Investigating MMPs' role in regulating cancer cell phenotype is critical for understanding invasion.
Purpose of the Study:
- To investigate the role of matrix metalloproteinase (MMP) catalytic activity in modulating cancer cell biophysical properties relevant to invasion.
- To elucidate the molecular mechanisms by which MMPs influence cancer cell spreading, motility, contractility, and stiffness.
Main Methods:
- Utilized biochemical assays to probe MMP catalytic activity.
- Employed biophysical measurements to assess cancer cell spreading, motility, contractility, and cortical stiffness.
- Investigated the role of integrins and focal adhesion kinase (FAK) in MMP-mediated cellular changes.
- Compared cellular responses on native versus MMP pre-conditioned surfaces.
Main Results:
- MMP catalytic activity was found to regulate cancer cell spreading, motility, contractility, and cortical stiffness.
- MMP activity stabilizes integrins at the cell membrane and activates focal adhesion kinase (FAK).
- Inhibition of MMPs induced cell rounding and softening on stiff gels, an effect reduced on MMP pre-conditioned surfaces.
Conclusions:
- MMP catalytic activity plays a significant role in regulating the invasiveness of cancer cells.
- MMP-mediated modulation of integrin function is a key mechanism controlling cancer cell biophysical properties and invasion.
- Understanding MMPs' influence on cell mechanics offers potential therapeutic targets for cancer treatment.
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