Emerging role of DUBs in tumor metastasis and apoptosis: Therapeutic implication.
Emerging role of DUBs in tumor metastasis and apoptosis: Therapeutic implication.
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配音在肿瘤转移和凋亡中的新兴作用：治疗意义。
DOI：
10.1016/j.pharmthera.2017.03.001
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发表时间：
2017-09
影响因子：
13.5
通讯作者：
Wan Y
中科院分区：
文献类型：
--
作者：
He M;Zhou Z;Wu G;Chen Q;Wan Y
泛素-蛋白酶体系统的功能障碍与肿瘤的形成和转移密切相关。靶向泛素通路为抗癌治疗提供了新的策略。尽管泛素修饰剂起着一定的作用，但通过去泛素化酶（DUBs）将泛素从功能蛋白中去除在转移级联的多个步骤中起着重要作用，包括肿瘤的局部侵袭、传播和最终定植到远处器官。无调控的泛素化和去泛素化都可能导致细胞凋亡和上皮间质转化（EMT）等多种关键事件和途径的失调。最近的TCGA研究进一步揭示了dub突变与各种类型肿瘤之间的联系。此外，针对DUBs的新药物设计为抗癌治疗提供了新的策略。在这篇综述中，我们将总结去泛素化的作用，并重点介绍DUBs在多种转移事件中的最新发现，包括抗凋亡途径和EMT。我们将进一步讨论去泛素化调控作为抗癌治疗的新策略。
Malfunction of ubiquitin-proteasome system is tightly linked to tumor formation and tumor metastasis. Targeting the ubiquitin-pathway provides a new strategy for anti-cancer therapy. Despite the parts played by ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in governing the multiple steps of the metastatic cascade, including local invasion, dissemination, and eventual colonization of the tumor to distant organs. Both deregulated ubiquitination and deubiquitination could lead to dysregulation of various critical events and pathways such as apoptosis and epithelial-mesenchymal transition (EMT). Recent TCGA study has further revealed the connection between mutations of DUBs and various types of tumors. In addition, emerging drug design targeting DUBs provides a new strategy for anti-cancer therapy. In this review, we will summarize the role of deubiquitination and highlight the recent discoveries of DUBs with regards to multiple metastatic events including anti-apoptosis pathway and EMT. We will further discuss the regulation of deubiquitination as a novel strategy for anti-cancer therapy.
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