Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets alpha1-antitrypsin serpin.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Source:
      Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Print ISSN: 0008-5472 (Print) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE
    • Publication Information:
      Publication: Baltimore, Md. : American Association for Cancer Research
      Original Publication: Chicago [etc.]
    • Subject Terms:
    • Abstract:
      Proteases exert control over cell behavior and affect many biological processes by making proteolytic modification of regulatory proteins. The purpose of this paper is to describe novel, important functions of matrix metalloproteinase (MMP)-26. alpha1-Antitrypsin (AAT) is a serpin, the primary function of which is to regulate the activity of neutrophil/leukocyte elastase. Insufficient antiprotease activity because of AAT deficiency in the lungs is a contributing factor to early-onset emphysema. We recently discovered that AAT is efficiently cleaved by a novel metalloproteinase, MMP-26, which exhibits an unconventional PH(81)CGVPD Cys switch motif and is autocatalytically activated in cells and tissues. An elevated expression of MMP-26 in macrophages and polymorphonuclear leukocytes supports the functional role of MMP-26 in the AAT cleavage and inflammation. We have demonstrated a direct functional link of MMP-26 expression with an estrogen dependency and confirmed the presence of the estrogen-response element in the MMP-26 promoter. Immunostaining of tumor cell lines and biopsy specimen microarrays confirmed the existence of the inverse correlations of MMP-26 and AAT in cells/tissues. An expression of MMP-26 in the estrogen-dependent neoplasms is likely to contribute to the inactivation of AAT, to the follow-up liberation of the Ser protease activity, and because of these biochemical events, to promote matrix destruction and malignant progression. In summary, we hypothesize that MMP-26, by cleaving and inactivating the AAT serpin, operates as a unique functional link that regulates a coordinated interplay between Ser and metalloproteinases in estrogen-dependent neoplasms.
    • Grant Information:
      CA77470 United States CA NCI NIH HHS; CA83017 United States CA NCI NIH HHS
    • Accession Number:
      0 (Estrogens)
      0 (Receptors, Estrogen)
      0 (Recombinant Proteins)
      0 (alpha 1-Antitrypsin)
      EC 3.4.24.- (MMP26 protein, human)
      EC 3.4.24.- (Matrix Metalloproteinases)
      EC 3.4.24.- (Matrix Metalloproteinases, Secreted)
    • Publication Date:
      Date Created: 20041203 Date Completed: 20050127 Latest Revision: 20071114
    • Publication Date:
      20221213
    • Accession Number:
      10.1158/0008-5472.CAN-04-3019
    • Accession Number:
      15574774