Department of Chemoradiotherapy, The Affiliated People's Hospital of Ningbo University, Ningbo, 315040, China.
Department of Otolaryngology-Head and Neck Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, 315040, China.
J Mol Med (Berl). 2023 Dec;101(12):1543-1565. doi: 10.1007/s00109-023-02376-7. Epub 2023 Oct 5.
Nasopharyngeal carcinoma (NPC) is one of the most common squamous cell carcinomas of the head and neck, and Epstein-Barr virus (EBV) infection is one of the pathogenic factors involved in the oncogenetic development and progression of NPC. E3 ligases, which are key members of the ubiquitin proteasome system (UPS), specifically recognize various oncogenic factors and tumor suppressors and contribute to determining their fate through ubiquitination. Several studies have demonstrated that E3 ligases are aberrantly expressed and mutated in NPC and that these changes are closely associated with the occurrence and progression of NPC. Herein, we aim to thoroughly review the specific action mechanisms by which E3 ligases participate in NPC signaling pathways and discuss their functional relationship with EBV. Moreover, we describe the current progress in and limitations for targeted therapies against E3 ligases in NPC. KEY MESSAGES: • E3 ubiquitin ligases, as members of the UPS system, determine the fate of their substrates and may act either as oncogenic or anti-tumorigenic factors in NPC. • Mutations or dysregulated expression of E3 ubiquitin ligases is closely related to the occurrence, development, and therapeutic sensitivity of NPC, as they play important roles in several signaling pathways affected by EBV infection. • As promising therapeutic targets, E3 ligases may open new avenues for treatment and for improving the prognosis of NPC patients.
鼻咽癌（NPC）是头颈部最常见的鳞状细胞癌之一，EBV 感染是 NPC 癌基因发生和发展的致病因素之一。E3 连接酶是泛素蛋白酶体系统（UPS）的关键成员，特异性识别各种致癌因子和肿瘤抑制因子，并通过泛素化作用决定它们的命运。多项研究表明，E3 连接酶在 NPC 中表达异常和突变，这些变化与 NPC 的发生和发展密切相关。本文旨在全面综述 E3 连接酶参与 NPC 信号通路的具体作用机制，并探讨其与 EBV 的功能关系。此外，还描述了针对 NPC 中 E3 连接酶的靶向治疗的最新进展和局限性。关键信息：• E3 泛素连接酶作为 UPS 系统的成员，决定其底物的命运，在 NPC 中可能作为致癌或抑癌因子发挥作用。• E3 泛素连接酶的突变或表达失调与 NPC 的发生、发展和治疗敏感性密切相关，因为它们在 EBV 感染影响的几个信号通路中发挥重要作用。• 作为有前途的治疗靶点，E3 连接酶可能为 NPC 患者的治疗和改善预后开辟新途径。
