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Aberrant, persistent inclusion into lipid rafts limits the tumorigenic function of membrane type-1 matrix metalloproteinase in malignant cells

Academic Article
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Overview

authors

  • Rozanov, D. V.
  • Deryugina, Elena
  • Monosov, E. Z.
  • Marchenko, N. D.
  • Strongin, A. Y.

publication date

  • February 2004

journal

  • Experimental Cell Research  Journal

abstract

  • Membrane type-1 matrix metalloproteinase (MT1-MMP) is a key enzyme in cell locomotion and tissue remodeling. Trafficking to the plasma membrane and internalization into the transient storage compartment both regulate the cell surface presentation of MT1-MMP. Our data indicate that mutant MT1-MMP lacking the cytoplasmic tail is recruited to the caveolae-enriched lipid raft membrane microdomains in breast carcinoma MCF7 cells. In contrast, the wild-type protease is not permanently associated with lipid rafts. Trafficking to lipid rafts correlated with poor internalization and the persistent presentation of MT1-MMP at the cell surface. The tail mutant efficiently functioned in inducing the activation of the latent proMMP-2 zymogen, matrix remodeling, and contraction of three-dimensional collagen lattices. Recruitment of the tail mutant to lipid raft antagonized, however, the cleavage of the plasma membrane-associated E-cadherin. These events limited the contribution of the tail mutant to cell locomotion and malignant growth. It is conceivable that the tail peptide sequence plays a crucial role in the translocations of MT1-MMP across the cell and contributes to coordinated cellular functions. It is tempting to hypothesize that the mechanisms involved in trafficking of MT1-MMP to caveolin-enriched lipid rafts may be targeted in a clinically advantageous manner.

subject areas

  • Amino Acid Substitution
  • Animals
  • Breast Neoplasms
  • Cadherins
  • Carcinoma
  • Cell Adhesion
  • Cell Aggregation
  • Cell Line, Tumor
  • Cell Movement
  • Cell Transplantation
  • Collagen
  • Enzyme Activation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma
  • Humans
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinases, Membrane-Associated
  • Membrane Microdomains
  • Metalloendopeptidases
  • Mice
  • Mice, Nude
  • Neoplasms
  • Transplantation, Heterologous
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Research

keywords

  • breast carcinoma
  • caveolin
  • extracellular matrix
  • glioblastoma
  • invasion
  • lipid rafts
  • migration
  • xenografts
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Identity

International Standard Serial Number (ISSN)

  • 0014-4827

Digital Object Identifier (DOI)

  • 10.1016/j.yexer.2003.10.006

PubMed ID

  • 14729059
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Additional Document Info

start page

  • 81

end page

  • 95

volume

  • 293

issue

  • 1

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