Peduto Lucie
Institut Pasteur, Laboratory of Lymphoid Tissue Development, CNRS URA1961, Paris, France.
Curr Pharm Des. 2009;15(20):2282-7. doi: 10.2174/138161209788682415.
ADAM (a disintegrin and metalloproteinase) proteins have a predominant role in the protein ectodomain shedding of membrane-bound molecules. ADAMs have emerged as critical regulators of cell-cell signaling during development and homeostasis, and are believed to contribute to pathologies, such as cancer, where their regulation is altered. ADAM9 is consistently overexpressed in various human cancers, and plays a role in tumorigenesis in mouse models. ADAM9 cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as EGF, FGFR2iiib, Tie-2, Flk-1, EphB4, CD40, VCAM-1, and VE-cadherin, and could represent a potential therapeutic target in tumors where it is highly expressed. This review provides an overview of ADAM9 with a major focus on its contribution to tumorigenesis. Its role in the shedding of cell surface molecules will be discussed along with emerging aspects of regulation and possible functions in cancer development.
ADAM（一种解整合素和金属蛋白酶）蛋白在膜结合分子的蛋白质胞外域脱落过程中起主要作用。ADAM已成为发育和体内平衡过程中细胞间信号传导的关键调节因子，并且被认为与癌症等病理状况有关，在这些病理状况中其调节发生改变。ADAM9在多种人类癌症中持续过度表达，并在小鼠模型的肿瘤发生中发挥作用。ADAM9切割并释放多种在肿瘤发生和血管生成中起重要作用的分子，如表皮生长因子（EGF）、成纤维细胞生长因子受体2亚型b（FGFR2iiib）、酪氨酸激酶受体2（Tie-2）、血管内皮生长因子受体1（Flk-1）、红细胞生成素受体B4（EphB4）、肿瘤坏死因子受体超家族成员40（CD40）、血管细胞黏附分子1（VCAM-1）和血管内皮钙黏蛋白（VE-cadherin），并且在其高表达的肿瘤中可能代表一个潜在的治疗靶点。本综述概述了ADAM9，主要关注其对肿瘤发生的贡献。将讨论其在细胞表面分子脱落中的作用以及癌症发展中调节和可能功能的新方面。
