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ADAM (a disintegrin and metalloproteinase) proteases as potential<br />
cancer therapeutic targets<br />
Dylan R. Edwards<br />
Biomedical Research Centre, School <strong>of</strong> Biological Sciences, University <strong>of</strong> East Anglia, Norwich, NR4 7TJ,<br />
UK<br />
Adamalysins (a disintegrin and metalloproteinase, ADAMs) are a family <strong>of</strong> cell surface<br />
transmembrane proteins that have broad biological functions encompassing proteolysis,<br />
adhesion and cell signal regulation. Several function as “ectodomain sheddases” that are<br />
responsible for the proteolytic release or activation <strong>of</strong> membrane associated ligands and<br />
receptors. In particular, ADAM-17 (tumour necrosis factor-α converting enzyme, TACE)<br />
is involved in the activation <strong>of</strong> pro-TNF-α and has an essential developmental role in<br />
regulating the biological functions <strong>of</strong> ligands <strong>of</strong> the epidermal growth factor receptor<br />
(EGFR). ADAM-10 also has a prominent role in Notch signaling. I will review current<br />
knowledge <strong>of</strong> the roles <strong>of</strong> ADAM proteins in cancer biology, and focus on recent work<br />
from our group that has linked ADAM-15 with clinical aggressiveness in breast cancer.<br />
The potential for selective targeting <strong>of</strong> ADAM proteins will also be discussed.<br />
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