Abstract
Both cancer and chronic inflammatory diseases are often marked by homeostatic signal transduction pathways run amok. Cleavage of membrane-bound substrates by extracellular metalloproteinases is frequently the rate limiting step in activating many of these pathways, resulting either in liberation of active ligands (shedding) or initiating further processing into bioactive cytoplasmic domains (regulated intramembrane proteolysis or RIP). ADAM10 is a member of the ADAM (A Disintegrin And Metalloproteinase) family of transmembrane metalloproteinases implicated in the RIPing and shedding of dozens of substrates that drive cancer progression and inflammatory disease, including Notch, E-cadherin, EGF, ErbB2 and inflammatory cytokines. ADAM10s emerging role as a significant contributor to these pathologies has led to intense interest in it as a potential drug target for disease treatment. Here we discuss some of the established functions of ADAM10 and the implications of its inhibition in disease progression.
Keywords: ADAM10, disintegrin, metalloproteinase, inhibition, cancer, inflammation, erbB, Notch, signaling, CD44
Current Pharmaceutical Design
Title: ADAM10 as a Therapeutic Target for Cancer and Inflammation
Volume: 15 Issue: 20
Author(s): Howard C. Crawford, Peter J. Dempsey, Gordon Brown, Liana Adam and Marcia L. Moss
Affiliation:
Keywords: ADAM10, disintegrin, metalloproteinase, inhibition, cancer, inflammation, erbB, Notch, signaling, CD44
Abstract: Both cancer and chronic inflammatory diseases are often marked by homeostatic signal transduction pathways run amok. Cleavage of membrane-bound substrates by extracellular metalloproteinases is frequently the rate limiting step in activating many of these pathways, resulting either in liberation of active ligands (shedding) or initiating further processing into bioactive cytoplasmic domains (regulated intramembrane proteolysis or RIP). ADAM10 is a member of the ADAM (A Disintegrin And Metalloproteinase) family of transmembrane metalloproteinases implicated in the RIPing and shedding of dozens of substrates that drive cancer progression and inflammatory disease, including Notch, E-cadherin, EGF, ErbB2 and inflammatory cytokines. ADAM10s emerging role as a significant contributor to these pathologies has led to intense interest in it as a potential drug target for disease treatment. Here we discuss some of the established functions of ADAM10 and the implications of its inhibition in disease progression.
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Cite this article as:
Crawford C. Howard, Dempsey J. Peter, Brown Gordon, Adam Liana and Moss L. Marcia, ADAM10 as a Therapeutic Target for Cancer and Inflammation, Current Pharmaceutical Design 2009; 15 (20) . https://dx.doi.org/10.2174/138161209788682442
DOI https://dx.doi.org/10.2174/138161209788682442 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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