The ADAMs family of proteases: new biomarkers and therapeutic targets for cancer?
The ADAMs family of proteases: new biomarkers and therapeutic targets for cancer?
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DOI：
10.1186/1559-0275-8-9
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发表时间：
2011-06-09
影响因子：
3.8
通讯作者：
McGowan PM
中科院分区：
文献类型：
--
作者：
Duffy MJ;Mullooly M;O'Donovan N;Sukor S;Crown J;Pierce A;McGowan PM
亚当斯是涉及蛋白水解和细胞粘附的跨膜蛋白。该家族的40个基因成员已被鉴定，其中21个被认为在人类中具有功能。作为蛋白酶，它们的主要底物是其他跨膜蛋白的胞外域。这些底物包括生长因子、细胞因子、生长因子受体、细胞因子受体和几种不同类型的粘附分子的前体形式。虽然特定亚当斯的表达改变与不同疾病有关，但它们在癌症形成和进展中的作用最有据可查。在癌症中发挥作用的亚当斯包括ADAM 9、ADAM 10、ADAM 12、ADAM 15和ADAM 17。两个亚当斯，即，ADAM 10和17似乎通过释放HER/EGFR配体促进癌症进展。释放的配体激活HER/EGFR信号传导，最终导致细胞增殖、迁移和存活增加。与癌症中的致病作用一致，几种亚当斯正在成为帮助癌症诊断和预测患者结果的潜在癌症生物标志物。此外，许多选择性ADAM抑制剂，特别是针对ADAM 10和ADAM 17的选择性ADAM抑制剂，已被证明具有抗癌作用。这些抑制剂中至少有一种正在乳腺癌患者中进行临床试验。
The ADAMs are transmembrane proteins implicated in proteolysis and cell adhesion. Forty gene members of the family have been identified, of which 21 are believed to be functional in humans. As proteases, their main substrates are the ectodomains of other transmembrane proteins. These substrates include precursor forms of growth factors, cytokines, growth factor receptors, cytokine receptors and several different types of adhesion molecules. Although altered expression of specific ADAMs has been implicated in different diseases, their best-documented role is in cancer formation and progression. ADAMs shown to play a role in cancer include ADAM9, ADAM10, ADAM12, ADAM15 and ADAM17. Two of the ADAMs, i.e., ADAM10 and 17 appear to promote cancer progression by releasing HER/EGFR ligands. The released ligands activate HER/EGFR signalling that culminates in increased cell proliferation, migration and survival. Consistent with a causative role in cancer, several ADAMs are emerging as potential cancer biomarkers for aiding cancer diagnosis and predicting patient outcome. Furthermore, a number of selective ADAM inhibitors, especially against ADAM10 and ADAM17, have been shown to have anti-cancer effects. At least one of these inhibitors is now undergoing clinical trials in patients with breast cancer.