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ADAM15 as an Emerging Cancer Target

In addition to its role in the vasculature, ADAM15 is also associated with the progression of several adenocarcinomas. Clinical studies have identified that ADAM15 expression is elevated in the aggressive forms of prostate and breast cancers correlating strongly with Gleason score and angioscore respectively (1). Studies have identified a potential role for ADAM15 in mediating metastatic progression through enhancing tumour cell-endothelial cell adhesion and vessel intravasation (2). Shedding of E-cadherin on tumour cells by ADAM15 has also been postulated to play a role in breast cancer cell signalling via EGF/Her pathway (3). Furthermore, a Src-binding, cytoplasmic splice variant of ADAM15 associated with an aggressive form of breast cancer was shown to have enhanced catalytic activity (4). Therefore, the dual role of ADAM15 in promoting angiogenesis and cancer progression suggests that targeting ADAM15 in these cancers may have the added benefit of disrupting several processes contributing to the tumour burden and provide early insight into which cancer subtypes might prove most responsive to anti-ADAM15 therapy (5).


  1. Kuefer, R., Day, KC., Kleer, CG., Sabel, MS et al. (2006). ADAM15 Disintegrin is associated with aggressive prostrate and breast cancer. Neoplasia 8, 319-329.
  2. Najy, AJ., Day, KC. And Day, ML (2008). ADAM15 supports prostate cancer metastasis by modulating tumour cell-endothelial cell interaction. Cancer Res. 68, 1092-1099.
  3. Abdo J. Najy, Kathleen C. Day and Mark L. Day (2008).The Ectodomain Shedding of E-cadherin by ADAM15 Supports ErbB Receptor Activation J. Biol Chem. 283, 18393-18401.
  4. Maretzky T, Le Gall SM, Worpenberg-Pietruk S, Eder J, Overall CM, Huang XY, Poghosyan Z, Edwards DR, Blobel CP. (2009). Src stimulates fibroblast growth factor receptor-2 shedding by an ADAM15 splice variant linked to breast cancer. Cancer Res. 1;69(11):4573-6.
  5. Lucas N, Day ML. (2009).The role of the disintegrin metalloproteinase ADAM15 in prostate cancer progression. J Cell Biochem. 106(6):967-74.