An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase

Boris I. Ratnikov, Dmitri V. Rozanov, Tanya I. Postnova, Peter G. Baciu, Heying Zhang, Richard G. Discipio, Galina G. Chestukhina, Jeffrey W. Smith, Elena I. Deryugina, Alex Y. Strongin

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129 Scopus citations

Abstract

Membrane type-1 matrix metalloproteinase (MT1-MMP) and αvβ3 integrin are both essential to cell invasion. Maturation of integrin pro-αv chain (pro-αv) involves its cleavage by proprotein convertases (PC) to form the disulfide-bonded 125-kDa heavy and 25-kDa light α chains. Our report presents evidence of an alternative pathway of pro-αv processing involving MT1-MMP. In breast carcinoma MCF7 cells deficient in MT1-MMP, pro-αv is processed by a conventional furin-like PC, and the mature αv integrin subunit is represented by the 125-kDa heavy chain and the 25-kDa light chain commencing from the N-terminal Asp891. In contrast, in cells co-expressing αvβ3 and MT1-MMP, MT1-MMP functions as an integrin convertase. MT1-MMP specifically cleaves pro-αv, generating a 115-kDa heavy chain with the truncated C terminus and a 25-kDa light chain commencing from the N-terminal Leu892. PC-cleavable α3 and α5 but not the PC-resistant α2 integrin subunit are also susceptible to MT1-MMP cleavage. These novel mechanisms involved in the processing of integrin α subunits underscore the significance and complexity of interactions between MT1-MMP and adhesion receptors and suggest that regulation of integrin functionality may be an important role of MT1-MMP in migrating tumor cells.

Original languageEnglish (US)
Pages (from-to)7377-7385
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number9
DOIs
StatePublished - Mar 1 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ratnikov, B. I., Rozanov, D. V., Postnova, T. I., Baciu, P. G., Zhang, H., Discipio, R. G., Chestukhina, G. G., Smith, J. W., Deryugina, E. I., & Strongin, A. Y. (2002). An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase. Journal of Biological Chemistry, 277(9), 7377-7385. https://doi.org/10.1074/jbc.M109580200