Modulation of Breast Cancer Cell Function by Intracellular Signaling Through the Membrane-Type I Matrix Metalloproteinase

Abstract

Membrane-type 1 matrix metalloproteinase (MT1 -MMP), a transmembrane proteinase with the catalytic domain exposed on the cell surface and a short cytoplasmic domain, has been implicated in the aggressiveness of a variety of human malignancies including mammary carcinoma. MT1-MMP forms a tri-molecular complex with matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2), an interaction required for MMP-2 activation. Whereas the extracellular proteolytic activity of MT1 -MMP represents a proteolytic mechanism of tumor progression, its non- catalytic, cytoplasmic domain may serve as a transducer of intracellular signaling through a proteolysis-independent mechanism(s). This project aims to test the hypothesis that MT1-MMP binding of MMP-2 and/or TIMP-2 generates intracellular signaling through the cytoplasmic domain of MT1-MMP and thus regulates cell functions involved in breast carcinoma progression.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2000
Accession Number
ADA388961

Entities

People

  • Paolo Mignatti

Organizations

  • New York University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Anti-Bacterial Agents
  • Aprotinin
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Membrane
  • Cells
  • Culture Media
  • Culture Techniques
  • Degradation
  • Gene Expression
  • Inhibitors
  • Neoplasms
  • Proteins
  • Tissues
  • Tumor Cell Line

Fields of Study

  • Biology
  • Chemistry
  • Computer science

Readers

  • Molecular Biology and Genetics