A growing amount of evidence indicates that the neuronally expressed developmentally downregulated 4 (NEDD4, also known as NEDD4-1) E3 ligase plays a critical role in a variety of cellular processes via the ubiquitination-mediated degradation of multiple substrates. The abnormal regulation of NEDD4 protein has been implicated in cancer development and progression. In this review article, we briefly delineate the downstream substrates and upstream regulators of NEDD4, which are involved in carcinogenesis. Moreover, we succinctly elucidate the functions of NEDD4 protein in tumorigenesis and progression, including cell proliferation, apoptosis, cell cycle, migration, invasion, epithelial mesenchymal transition (EMT), cancer stem cells, and drug resistance. The findings regarding NEDD4 functions are further supported by knockout mouse models and human tumor tissue studies. This review could provide a promising and optimum anticancer therapeutic strategy via targeting the NEDD4 protein.

越来越多的证据表明，神经元表达的发育下调 4（NEDD4，也称为 NEDD4-1）E3 连接酶通过泛素化介导的多种底物降解在各种细胞过程中发挥关键作用。NEDD4 蛋白的异常调节与癌症的发展和进展有关。在这篇综述文章中，我们简要描述了 NEDD4 的下游底物和上游调节剂，它们与致癌作用有关。此外，我们简洁地阐明了 NEDD4 蛋白在肿瘤发生和进展中的功能，包括细胞增殖、凋亡、细胞周期、迁移、侵袭、上皮间充质转化 (EMT)、癌症干细胞和耐药性。关于 NEDD4 功能的发现得到了敲除小鼠模型和人类肿瘤组织研究的进一步支持。该综述可以通过靶向 NEDD4 蛋白提供一种有前途和最佳的抗癌治疗策略。