Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 71, Issue 4, Pages 659-672Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-013-1457-3
Keywords
Tissue inhibitor of metalloproteinases; TIMP-1 signaling pathway; CD63; Let-7f miRNA; Cell growth; Apoptosis; Cell differentiation; Cancer
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Funding
- Institute of Cardiovascular Prevention, Ludwig-Maximilians-University of Munich
- German Federal Ministry of Defense [M/SABX/8A002]
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The tissue inhibitors of metalloproteinases (TIMPs) are well recognized for their role in extracellular matrix remodeling by controlling the activity of matrix metalloproteinases (MMPs). Independent of MMP inhibition, TIMPs act as signaling molecules with cytokine-like activities thereby influencing various biological processes including cell growth, apoptosis, differentiation, angiogenesis, and oncogenesis. Recent studies on TIMP-1's cytokine functions have identified complex regulatory networks involving a specific surface receptor and subsequent signaling pathways including miRNA-mediated posttranscriptional regulation of gene expression that ultimately control the fate and behavior of the cells. The present review summarizes the current knowledge on TIMP-1 as a cytokine modulator of cell functions, outlines recent progress in defining molecular pathways that transmit TIMP-1 signals from the cell periphery into the nucleus, and discusses TIMP-1's role as a cytokine in the pathophysiology of cancer and other human diseases.
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