Guo Qianqian, Qin Hai, Chen Zelong, Zhang Wenzhou, Zheng Lufeng, Qin Tingting
Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, China.
Department of Clinical Laboratory, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou 550014, China.
Genes Dis. 2024 Apr 17;12(3):101311. doi: 10.1016/j.gendis.2024.101311. eCollection 2025 May.
The ubiquitin (Ub) system, a ubiquitous presence across eukaryotes, plays a crucial role in the precise orchestration of diverse cellular protein processes. From steering cellular signaling pathways and orchestrating cell cycle progression to guiding receptor trafficking and modulating immune responses, this process plays a crucial role in regulating various biological functions. The dysregulation of Ub-mediated signaling pathways in prevalent cancers ushers in a spectrum of clinical outcomes ranging from tumorigenesis and metastasis to recurrence and drug resistance. Ubiquitination, a linchpin process mediated by Ub, assumes a central mantle in molding cellular signaling dynamics. It navigates transitions in biological cues and ultimately shapes the destiny of proteins. Recent years have witnessed an upsurge in the momentum surrounding the development of protein-based therapeutics aimed at targeting the Ub system under the sway of cancer stem cells. The article provides a comprehensive overview of the ongoing in-depth discussions regarding the regulation of the Ub system and its impact on the development of cancer stem cells. Amidst the tapestry of insights, the article delves into the expansive roles of E3 Ub ligases, deubiquitinases, and transcription factors entwined with cancer stem cells. Furthermore, the spotlight turns to the interplay with pivotal signaling pathways the Notch, Hedgehog, Wnt/β-catenin, and Hippo-YAP signaling pathways all play crucial roles in the regulation of cancer stem cells followed by the specific modulation of Ub-proteasome.
泛素（Ub）系统在真核生物中普遍存在，在精确协调各种细胞蛋白质过程中发挥着关键作用。从调控细胞信号通路、协调细胞周期进程到引导受体运输和调节免疫反应，这一过程在调节各种生物学功能中起着至关重要的作用。在常见癌症中，Ub介导的信号通路失调会引发一系列临床后果，从肿瘤发生和转移到复发和耐药。泛素化是由Ub介导的关键过程，在塑造细胞信号动态中占据核心地位。它引导生物信号的转变，并最终决定蛋白质的命运。近年来，在癌症干细胞的影响下，针对Ub系统的基于蛋白质的治疗药物的开发势头激增。本文全面概述了关于Ub系统调控及其对癌症干细胞发育影响的正在进行的深入讨论。在众多见解中，本文深入探讨了与癌症干细胞相关的E3泛素连接酶、去泛素化酶和转录因子的广泛作用。此外，焦点转向与关键信号通路的相互作用——Notch、Hedgehog、Wnt/β-连环蛋白和Hippo-YAP信号通路在癌症干细胞的调控中都起着关键作用，随后是对Ub蛋白酶体的特异性调节。
