TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance

Int J Biol Sci. 2024 Jan 1;20(1):182-199. doi: 10.7150/ijbs.87180. eCollection 2024.

Abstract

Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. Despite continuous improvement in treatment strategies, recurrence or persistence of cancer after radiotherapy is still inevitable, highlighting the need to identify therapeutic resistance factors and develop effective methods for NPC treatment. Herein, we found that TRAF4 is overexpressed in NPC cells and tissues. Knockdown TRAF4 significantly increased the radiosensitivity of NPC cells, possibly by inhibiting the Akt/Wee1/CDK1 axis, thereby suppressing survivin phosphorylation and promoting its degradation by FBXL7. TRAF4 is positively correlated with p-Akt and survivin in NPC tissues. High protein levels of TRAF4 were observed in acquired radioresistant NPC cells, and knockdown of TRAF4 overcomes radioresistant in vitro and the xenograft mouse model. Altogether, our study highlights the TRAF4-survivin axis as a potential therapeutic target for radiosensitization in NPC.

Keywords: Nasopharyngeal carcinoma; Radioresistance; Survivin; TRAF4; Ubiquitination.

MeSH terms

  • Animals
  • Carcinoma* / pathology
  • Humans
  • Mice
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / radiotherapy
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / metabolism
  • Nasopharyngeal Neoplasms* / radiotherapy
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Survivin / genetics
  • Survivin / metabolism
  • TNF Receptor-Associated Factor 4 / metabolism
  • Ubiquitination / genetics

Substances

  • Proto-Oncogene Proteins c-akt
  • Survivin
  • TNF Receptor-Associated Factor 4
  • TRAF4 protein, human