E3 ubiquitin ligases in nasopharyngeal carcinoma and implications for therapies

J Mol Med (Berl). 2023 Dec;101(12):1543-1565. doi: 10.1007/s00109-023-02376-7. Epub 2023 Oct 5.

Abstract

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.

Keywords: E3 ubiquitin ligases; Epstein-Barr virus (EBV); Nasopharyngeal carcinoma (NPC); Targeted therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / pathology
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / metabolism
  • Humans
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms* / metabolism
  • Ubiquitin
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Ubiquitin-Protein Ligases
  • Ubiquitin