- Matrix metalloproteinase-3 (MMP-3), also known as stromelysin-1, plays an important role in the induction and progression of epithelial-to-mesenchymal transition (EMT), a biological process critical for tissue remodeling, wound healing, and pathological states like fibrosis and cancer metastasis.
- MMP-3 is an extracellular protease that degrades a variety of extracellular matrix (ECM) components, including collagens, laminin, fibronectin, and proteoglycans. By remodeling the ECM, MMP-3 disrupts the structural environment that maintains epithelial integrity, thereby facilitating changes in cell behavior associated with EMT.
- One of the hallmark features of EMT is the loss of E-cadherin, a cell-cell adhesion molecule crucial for maintaining epithelial polarity and structure. MMP-3 contributes to EMT by promoting the cleavage and downregulation of E-cadherin, weakening intercellular adhesion and enabling cells to detach and migrate.
- In addition to these structural effects, MMP-3 has been shown to activate key EMT transcription factors such as Snail, Slug, and Twist, which further repress E-cadherin expression and promote the expression of mesenchymal markers like vimentin and N-cadherin.
- Interestingly, MMP-3 can also induce reactive oxygen species (ROS) within cells, which contributes to genomic instability and may further promote EMT-associated gene expression. This dual ability to alter both the extracellular and intracellular environments makes MMP-3 a powerful inducer of EMT.
- In cancer, MMP-3 expression has been associated with increased cell motility, invasion, and metastasis. In the context of infection, particularly with Helicobacter pylori, the bacterial oncoprotein CagA has been shown to upregulate MMP-3, suggesting a possible mechanism by which chronic infection contributes to EMT and gastric carcinogenesis.
- Together, these findings highlight the central role of MMP-3 as a mediator that links environmental cues—whether inflammatory, infectious, or oncogenic—to the molecular events that drive EMT and disease progression.
