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蛋白酶在癌症中上皮-间充质细胞转化中的作用。

The role of proteases in epithelial-to-mesenchymal cell transitions in cancer.

机构信息

Institute of Molecular Medicine and Cell Research, University of Freiburg, 79104, Freiburg, Germany.

German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Heidelberg, partner site Freiburg, 79106, Freiburg, Germany.

出版信息

Cancer Metastasis Rev. 2019 Sep;38(3):431-444. doi: 10.1007/s10555-019-09808-2.

DOI:10.1007/s10555-019-09808-2
PMID:31482486
Abstract

Changing the characteristics of cells from epithelial states to mesenchymal properties is a key process involved in developmental and physiological processes as well as in many diseases with cancer as the most prominent example. Nowadays, a great deal of work and literature concerns the understanding of the process of epithelial-to-mesenchymal transition (EMT) in terms of its molecular regulation and its implications for cancer. Similar statements can certainly be made regarding the investigation of the more than 500 proteases typically encoded by a mammalian genome. Specifically, the impact of proteases on tumor biology has been a long-standing topic of interest. However, although EMT actively regulates expression of many proteases and proteolytic enzymes are clearly involved in survival, division, differentiation, and movements of cells, information on the diverse roles of proteases in EMT has been rarely compiled. Here we aim to conceptually connect the scientific areas of "EMT" and "protease" research by describing how several important classes of proteolytic enzymes are regulated by EMT and how they are involved in initiation and execution of the EMT program. To do so, we briefly introduce the evolving key features of EMT and its regulation followed by discussion of protease involvement in this process.

摘要

将细胞的特性从上皮状态改变为间充质特性是一个关键过程,涉及到发育和生理过程,以及许多疾病,其中癌症是最突出的例子。如今,大量的工作和文献都集中在理解上皮-间充质转化(EMT)的分子调控及其对癌症的影响。关于通常由哺乳动物基因组编码的 500 多种蛋白酶的研究,也可以做出类似的陈述。具体来说,蛋白酶对肿瘤生物学的影响一直是一个长期以来的研究课题。然而,尽管 EMT 积极调节许多蛋白酶的表达,而且蛋白酶在细胞的存活、分裂、分化和运动中显然都有参与,但关于蛋白酶在 EMT 中的多种作用的信息很少被汇总。在这里,我们旨在通过描述几种重要的蛋白水解酶类如何受 EMT 调控以及它们如何参与 EMT 程序的启动和执行,从概念上把“EMT”和“蛋白酶”研究这两个科学领域联系起来。为此,我们简要介绍了 EMT 的不断发展的关键特征及其调控,接着讨论了蛋白酶在这个过程中的参与。

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