ADAM10 as a therapeutic target for cancer and inflammation.
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.
Crawford
Howard C
HC
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
Dempsey
Peter J
PJ
Brown
Gordon
G
Adam
Liana
L
Moss
Marcia L
ML
D051722:ADAM Proteins / Q000187:drug effects*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008565:Membrane Proteins / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy*
D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human