Cysteine Cathepsins and the cutting edge of cancer invasion
Cysteine Cathepsins and the cutting edge of cancer invasion
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DOI：
10.4161/cc.6.1.3669
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发表时间：
2007-01-01
期刊：
影响因子：
4.3
通讯作者：
Joyce, Johanna A.
中科院分区：
文献类型：
--
作者：
Gocheva, Vasilena;Joyce, Johanna A.
半胱氨酸组织蛋白酶是溶酶体蛋白酶的一个家族，其在各种人类癌症中经常上调，并且已经涉及不同的肿瘤发生过程，如血管生成、增殖、凋亡和侵袭。在癌症进展过程中，组织蛋白酶通常易位到肿瘤细胞的细胞表面或分泌到细胞外环境中，在那里它们可以通过几种可能的机制促进肿瘤侵袭。首先，它们可以直接切割细胞外基质和基底膜的成分，基本上为肿瘤细胞从原发性肿瘤块迁移出去清除了一条路径。其次，在细胞膜上，组织蛋白酶可以引导蛋白水解级联，其中它们激活其他蛋白酶，如基质金属蛋白酶和尿激酶纤溶酶原激活剂，这反过来又促进入侵。最后，细胞粘附蛋白E-钙粘蛋白在细胞表面的裂解可以破坏粘附连接，从而促进癌细胞迁移和侵袭。因此，组织蛋白酶现在正在成为肿瘤进展的主要参与者，使其成为广泛人类癌症的潜在药物靶点。
Cysteine cathepsins are a family of lysosomal proteases that are often upregulated in various human cancers, and have been implicated in distinct tumorigenic processes such as angiogenesis, proliferation, apoptosis and invasion. During cancer progression, cathepsins are often translocated to the cell surface of tumor cells or are secreted into the extracellular milieu, where they can promote tumor invasion through several possible mechanisms. First, they can directly cleave components of the extracellular matrix and basement membrane, essentially clearing a path for the migration of tumor cells away from the primary tumor mass. Second, at the cell membrane, cathepsins can direct a proteolytic cascade in which they activate other proteases such as matrix metalloproteinases and urokinase plasminogen activator, which in turn promote invasion. Finally, cleavage of the cell adhesion protein, E-cadherin, at the cell surface can disrupt adherens junctions and thus facilitate cancer cell migration and invasion. Therefore, cathepsins are now emerging as major players in tumor progression, making them potential drug targets for a wide range of human cancers.