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Updated: Apr 29, 2026

Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
Published on: August 27, 2012
Molecular basis for MMP9 induction and disruption of epithelial cell-cell contacts by galectin-3
Jerome Mauris1, Ashley M Woodward1, Zhiyi Cao2
1Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Abstract:
Dynamic modulation of the physical contacts between neighboring cells is integral to epithelial processes such as tissue repair and cancer dissemination. Induction of matrix metalloproteinase (MMP) activity contributes to the disassembly of intercellular junctions and the degradation of the extracellular matrix, thus mitigating the physical constraint to cell movement. Using the cornea as a model, we show here that a carbohydrate-binding protein, galectin-3, promotes cell-cell detachment and redistribution of the tight junction protein occludin through its N-terminal polymerizing domain. Notably, we demonstrate that galectin-3 initiates cell-cell disassembly by inducing matrix metalloproteinase expression in a manner that is dependent on the interaction with and clustering of the matrix metalloproteinase inducer CD147 (also known as EMMPRIN and basigin) on the cell surface. Using galectin-3-knockout mice in an in vivo model of wound healing, we further show that increased synthesis of MMP9 at the leading edge of migrating epithelium is regulated by galectin-3. These findings establish a new galectin-3-mediated regulatory mechanism for induction of metalloproteinase expression and disruption of cell-cell contacts required for cell motility in migrating epithelia.
Insights
Galectin-3 binding protein promotes epithelial cell detachment by inducing matrix metalloproteinase (MMP) expression. This process is crucial for cell motility during tissue repair and cancer spread.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Dynamic cell-cell contact modulation is vital for epithelial functions like tissue repair and cancer metastasis.
- Matrix metalloproteinases (MMPs) degrade extracellular matrix and disrupt intercellular junctions, facilitating cell movement.
Purpose of the Study:
- To investigate the role of galectin-3 in regulating cell-cell detachment and MMP activity in epithelial tissues.
- To elucidate the molecular mechanism by which galectin-3 influences cell-cell adhesion and MMP induction.
Main Methods:
- Utilized the cornea as a model system.
- Investigated galectin-3's effect on cell-cell detachment and occludin redistribution.
- Examined galectin-3's interaction with CD147 (EMMPRIN) to induce MMP expression.
- Employed galectin-3-knockout mice for in vivo wound healing studies.
Main Results:
- Galectin-3, via its N-terminal domain, promotes epithelial cell detachment and occludin redistribution.
- Galectin-3 induces MMP expression through interaction and clustering of cell surface CD147.
- In vivo, galectin-3 regulates MMP9 synthesis at the leading edge of migrating epithelium during wound healing.
Conclusions:
- Established a novel galectin-3-mediated mechanism for inducing metalloproteinase expression.
- Demonstrated galectin-3's role in disrupting cell-cell contacts essential for epithelial cell motility.
- Highlighted galectin-3 as a key regulator in processes requiring epithelial cell migration.
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