Multiple roles for cysteine cathepsins in cancer
Multiple roles for cysteine cathepsins in cancer
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DOI：
10.4161/cc.3.12.1289
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发表时间：
2004-12-01
期刊：
影响因子：
4.3
通讯作者：
Hanahan, D
中科院分区：
文献类型：
--
作者：
Joyce, JA;Hanahan, D
半胱氨酸组织蛋白是近年来出现的一类在癌症中扮演重要角色的蛋白水解酶家族，并被广泛报道参与细胞凋亡、血管生成、细胞增殖和侵袭。在正常细胞中，半胱氨酸组织蛋白通常定位于溶酶体和其他细胞内，并参与蛋白质的降解和加工。然而，在某些肿瘤中，组织蛋白从细胞内转移到细胞表面，甚至可以分泌。此外，一些半胱氨酸组织蛋白的表达和活性水平在人类和小鼠癌症中上调。了解哪些组织蛋白是至关重要的，它们的底物是什么，以及它们可能如何在癌症中发挥这些复杂的作用，这是需要解决的重要问题。我们重点介绍了最近开始回答其中一些问题的结果，特别是从研究多阶段致癌的小鼠模型中得出的教训，这表明单个半胱氨酸组织蛋白在肿瘤进展中扮演着独特的角色。
Cysteine cathepsins are a family of proteases that have recently emerged as important players in cancer, and have variously been reported to be involved in apoptosis, angiogenesis, cell proliferation, and invasion. In normal cells, cysteine cathepsins are typically localized in lysosomes and other intracellular compartments, and are involved in protein degradation and processing. However, in certain tumors, cathepsins are translocated from their intracellular compartments to the cell surface, and can even be secreted. In addition, the expression and activity levels of some cysteine cathepsins are upregulated in human and mouse cancers. Understanding which cathepsins are critically involved, what their substrates are, and how they may be mediating these complex roles in cancer are important questions to address. We highlight recent results that begin to answer some of these questions, illustrating in particular the lessons from studying a mouse model of multistage carcinogenesis, which suggests distinctive roles for individual cysteine cathepsins in tumor progression.