靶向癌症干细胞中的去泛素化酶。
Targeting deubiquitinating enzymes in cancer stem cells.
作者信息
Lei Hu, Shan Huizhuang, Wu Yingli
机构信息
Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China.
出版信息
Cancer Cell Int. 2017 Nov 3;17:101. doi: 10.1186/s12935-017-0472-0. eCollection 2017.
Cancer stem cells (CSCs) are rare but accounted for tumor initiation, progression, metastasis, relapse and therapeutic resistance. Ubiquitination and deubiquitination of stemness-related proteins are essential for CSC maintenance and differentiation, even leading to execute various stem cell fate choices. Deubiquitinating enzymes (DUBs), specifically disassembling ubiquitin chains, are important to maintain the balance between ubiquitination and deubiquitination. In this review, we have focused on the DUBs regulation of stem cell fate determination. For example, we discuss deubiquitinase inhibition may lead stem cell transcription factors and CSCs-related protein degradation. Also, CSCs microenvironment is regulated by DUBs activity. Our review provides a new insight into DUBs activity by emphasizing their cellular role in regulating stem cell fate and illustrates the opportunities for the application of DUBs inhibitors in the CSC-targeted therapy.
癌症干细胞（CSCs）数量稀少，但却引发肿瘤起始、进展、转移、复发以及产生治疗抗性。干性相关蛋白的泛素化和去泛素化对于癌症干细胞的维持和分化至关重要，甚至可导致执行各种干细胞命运选择。去泛素化酶（DUBs）专门拆解泛素链，对于维持泛素化和去泛素化之间的平衡很重要。在本综述中，我们着重探讨了去泛素化酶对干细胞命运决定的调控作用。例如，我们讨论了去泛素化酶抑制可能导致干细胞转录因子和癌症干细胞相关蛋白降解。此外，癌症干细胞微环境受去泛素化酶活性的调控。我们的综述通过强调去泛素化酶在调节干细胞命运中的细胞作用，为去泛素化酶活性提供了新的见解，并阐明了去泛素化酶抑制剂在癌症干细胞靶向治疗中的应用机会。
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