Department of Pathology and Laboratory Medicine, St, Vincent's University Hospital, Dublin 4, Ireland.
Clin Proteomics. 2011 Jun 9;8(1):9. doi: 10.1186/1559-0275-8-9.
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.
ADAMs 是一种参与蛋白水解和细胞黏附的跨膜蛋白。该家族已鉴定出 40 个基因成员，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细胞外结构域。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黏附分子的前体形式。尽管特定 ADAMs 的表达改变与不同疾病有关，但它们最有文献记载的作用是在癌症的形成和发展中。已证明在癌症中起作用的 ADAMs 包括 ADAM9、ADAM10、ADAM12、ADAM15 和 ADAM17。两种 ADAMs，即 ADAM10 和 17，通过释放 HER/EGFR 配体似乎促进了癌症的进展。释放的配体激活 HER/EGFR 信号，最终导致细胞增殖、迁移和存活增加。与癌症中的因果作用一致，一些 ADAMs 作为辅助癌症诊断和预测患者预后的潜在癌症生物标志物正在出现。此外，已经证明一些选择性 ADAM 抑制剂，特别是针对 ADAM10 和 ADAM17 的抑制剂，具有抗癌作用。其中至少一种抑制剂目前正在接受乳腺癌患者的临床试验。
