Novel functions of TIMPs in cell signaling

Cancer Metastasis Rev. 2006 Mar;25(1):99-113. doi: 10.1007/s10555-006-7893-x.


Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases (MMPs) and the balance between MMPs/TIMPs regulates the extracellular matrix (ECM) turnover and remodeling during normal development and pathogenesis. Increasing evidence indicates a much more complex role for TIMPs during tumor progression and angiogenesis, in addition to their regulation of MMP-mediated ECM degradation. In this article, we review both the MMP-dependent and -independent actions of TIMPs for the regulation of cell death, cell proliferation, and angiogenesis, with a particular emphasis on TIMP-1 in the regulation of tetraspanin/integrin-mediated cell survival signal transduction pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Apoptosis
  • Cell Proliferation
  • Cell Survival
  • Disease Progression
  • Humans
  • Integrin beta1 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Mice
  • Models, Biological
  • Neoplasms / enzymology*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / metabolism
  • Platelet Membrane Glycoproteins / metabolism
  • Prognosis
  • Signal Transduction*
  • Tetraspanin 30
  • Tissue Inhibitor of Metalloproteinase-1 / physiology*
  • Tissue Inhibitor of Metalloproteinases / physiology*


  • Antigens, CD
  • CD63 protein, human
  • Cd63 protein, mouse
  • Integrin beta1
  • Matrix Metalloproteinase Inhibitors
  • Platelet Membrane Glycoproteins
  • Tetraspanin 30
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinases