ADAM10 as a Therapeutic Target for Cancer and Inflammation

被引：86

作者：

Crawford, Howard C. ^{[2
]}

Dempsey, Peter J. ^{[3
]}

Brown, Gordon ^{[4
]}

Adam, Liana ^{[4
]}

Moss, Marcia L. ^{[1
]}

机构：

[1] BioZyme Inc, Apex, NC 27523 USA

[2] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA

[3] Univ Michigan, Dept Pediat & Mol & Integrat Physiol, Ann Arbor, MI 48109 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Urol & Canc Biol, Houston, TX 77030 USA

来源：

CURRENT PHARMACEUTICAL DESIGN | 2009年 / 15卷 / 20期

关键词：

ADAM10; disintegrin; metalloproteinase; inhibition; cancer; inflammation; erbB; Notch; signaling; CD44; FasL; E-cadherin; CD23; Chemokine; TNF alpha; EPIDERMAL-GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; AMYLOID PRECURSOR PROTEIN; CELL-CELL ADHESION; REGULATED INTRAMEMBRANE PROTEOLYSIS; NOTCH SIGNALING PATHWAY; SOLUBLE FAS LIGAND; FC-EPSILON-RII; TNF-ALPHA; E-CADHERIN;

D O I：

10.2174/138161209788682442

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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. ADAM10's 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.

引用

页码：2288 / 2299

页数：12

共 156 条

[1]

The transmembrane CXC-chemokine ligand 16 is induced by IFN-γ and TNF-α and shed by the activity of the disintegrin-like metalloproteinase ADAM10 [J].