Processing of integrin αv subunit by membrane type 1 matrix metalloproteinase stimulates migration of breast carcinoma cells on vitronectin and enhances tyrosine phosphorylation of focal adhesion kinase

Elena I. Deryugina, Boris I. Ratnikov, Tanya I. Postnova, Dmitri V. Rozanov, Alex Y. Strongin

Research output: Contribution to journalArticle

177 Scopus citations

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 languageEnglish (US)
Pages (from-to)9749-9756
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number12
DOIs
StatePublished - Mar 22 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Processing of integrin α<sub>v</sub> subunit by membrane type 1 matrix metalloproteinase stimulates migration of breast carcinoma cells on vitronectin and enhances tyrosine phosphorylation of focal adhesion kinase'. Together they form a unique fingerprint.

  • Cite this