Abstract
Recently, we have shown that membrane type 1 matrix metalloproteinase (MT1-MMP) exhibits integrin convertase activity. Similar to furin-like proprotein convertases, MT1-MMP directly processes a single chain precursor of αv integrin subunit (pro-αv) into the heavy and light α-chains connected by a disulfide bridge. To evaluate functionality of MT1-MMP-processed integrins, we examined breast carcinoma MCF7 cells coexpressing αvβ3 integrin with either the wild type or mutant MT1-MMP in a variety of migration and adhesion tests. Specific inhibitors of proprotein convertases and MMP were employed in our cell system to attenuate the individual pathways of pro-αv maturation. We present evidence that MT1-MMP cleavage of pro-αv in the cells did not affect RGD-ligand binding of the resulting αvβ3 integrin but enhanced outside-in signal transduction through a focal adhesion kinase pathway. Enhanced tyrosine phosphorylation of focal adhesion kinase in cells co-expressing MT1-MMP and αvβ3 integrin contributed to efficient adhesion and, especially, migration of cells on vitronectin, a ligand of αvβ3 integrin. These mechanisms underscore the significance of a coordinated interplay between MT1-MMP and αvβ3 integrin in tumor cells and identify downstream signaling pathways resulting from their interactions. Regulation of integrin maturation and functionality may be an important role of MT1-MMP in tumor cells.
Original language | English (US) |
---|---|
Pages (from-to) | 9749-9756 |
Number of pages | 8 |
Journal | Journal of Biological Chemistry |
Volume | 277 |
Issue number | 12 |
DOIs | |
State | Published - Mar 22 2002 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology