Wang Yingshuang, Dai Jiawen, Zeng Youqin, Guo Jinlin, Lan Jie
Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Oncol. 2021 Oct 22;11:752604. doi: 10.3389/fonc.2021.752604. eCollection 2021.
Female breast cancer has become the most commonly occurring cancer worldwide. Although it has a good prognosis under early diagnosis and appropriate treatment, breast cancer metastasis drastically causes mortality. The process of metastasis, which includes cell epithelial-mesenchymal transition, invasion, migration, and colonization, is a multistep cascade of molecular events directed by gene mutations and altered protein expressions. Ubiquitin modification of proteins plays a common role in most of the biological processes. E3 ubiquitin ligase, the key regulator of protein ubiquitination, determines the fate of ubiquitinated proteins. E3 ubiquitin ligases target a broad spectrum of substrates. The aberrant functions of many E3 ubiquitin ligases can affect the biological behavior of cancer cells, including breast cancer metastasis. In this review, we provide an overview of these ligases, summarize the metastatic processes in which E3s are involved, and comprehensively describe the roles of E3 ubiquitin ligases. Furthermore, we classified E3 ubiquitin ligases based on their structure and analyzed them with the survival of breast cancer patients. Finally, we consider how our knowledge can be used for E3s' potency in the therapeutic intervention or prognostic assessment of metastatic breast cancer.
女性乳腺癌已成为全球最常见的癌症。尽管在早期诊断和适当治疗下预后良好，但乳腺癌转移会显著导致死亡。转移过程包括细胞上皮-间质转化、侵袭、迁移和定植，是由基因突变和蛋白质表达改变所引导的多步骤分子事件级联反应。蛋白质的泛素化修饰在大多数生物学过程中发挥着共同作用。E3泛素连接酶作为蛋白质泛素化的关键调节因子，决定了泛素化蛋白质的命运。E3泛素连接酶作用于广泛的底物。许多E3泛素连接酶的异常功能会影响癌细胞的生物学行为，包括乳腺癌转移。在本综述中，我们概述了这些连接酶，总结了E3泛素连接酶参与的转移过程，并全面描述了E3泛素连接酶的作用。此外，我们根据其结构对E3泛素连接酶进行分类，并分析它们与乳腺癌患者生存率的关系。最后，我们探讨如何将我们的知识应用于E3泛素连接酶在转移性乳腺癌治疗干预或预后评估中的效能。
