Membrane type-1 matrix metalloproteinase (MT1-MMP) processing of pro-alphav integrin regulates cross-talk between alphavbeta3 and alpha2beta1 integrins in breast carcinoma cells

We have recently demonstrated that in breast carcinoma MCF7 cells MT1-MMP processes the alphav, alpha3, and alpha5 integrin precursors generating the respective mature S-S-linked heavy and light alpha-chains. The precursor of alpha2 integrin subunit was found resistant to MT1-MMP proteolysis. The pr...

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Bibliographic Details
Published in:Experimental cell research 2003-11, Vol.291 (1), p.167-175
Main Authors: Baciu, Peter C, Suleiman, E Aisha, Deryugina, Elena I, Strongin, Alex Y
Format: Article
Language:English
Subjects:
Breast Neoplasms - metabolism
Carcinoma - metabolism
Cell Adhesion - physiology
Cell Line, Tumor
Cell Membrane - enzymology
Cell Movement - physiology
Collagen Type I - metabolism
Enzyme Precursors - metabolism
Extracellular Matrix - metabolism
Female
Humans
Integrin alpha2beta1 - metabolism
Integrin alphaVbeta3 - metabolism
Integrins - metabolism
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases - metabolism
Neoplasm Metastasis
Protein Processing, Post-Translational
Protein Subunits - metabolism
Receptor Cross-Talk - physiology
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Summary:We have recently demonstrated that in breast carcinoma MCF7 cells MT1-MMP processes the alphav, alpha3, and alpha5 integrin precursors generating the respective mature S-S-linked heavy and light alpha-chains. The precursor of alpha2 integrin subunit was found resistant to MT1-MMP proteolysis. The processing of the alphav subunit by MT1-MMP facilitated alphavbeta3-dependent adhesion, activation of FAK signaling pathway, and migration of MCF7 cells on vitronectin. To elucidate further the effects of MT1-MMP on cellular integrins, we examined the functional activity of alpha5beta1 and alpha2beta1 integrins in MCF7 cells expressing MT1-MMP. Either expression of MT1-MMP alone or its coexpression with alphavbeta3 failed to affect the functionality of alpha5beta1 integrin, and adhesion of cells to fibronectin. MT1-MMP, however, profoundly affected the cross-talk involving alphavbeta3 and alpha2beta1 integrins. In MT1-MMP-deficient cells, integrin alphavbeta3 suppressed the functional activity of the collagen-binding alpha2beta1 integrin receptor and diminished cell adhesion to type I collagen. Coexpression of MT1-MMP with integrin alphavbeta3 restored the functionality of alpha2beta1 integrin and, consequently, the ability of MCF7 cells to adhere efficiently to collagen. We conclude that the MT1-MMP-controlled cross-talk between alphavbeta3 and alpha2beta1 integrins supports binding of aggressive, MT1-MMP-, and alphavbeta3 integrin-expressing malignant cells on type I collagen, the most common substratum of the extracellular matrix.
ISSN:0014-4827