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Published on: May 23, 2025
TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance
Jinzhuang Liao1,2, Xiang Qing3, Xiaoying Li1,2
1Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
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.
Insights
Tumor necrosis factor receptor-associated factor 4 (TRAF4) is overexpressed in nasopharyngeal carcinoma (NPC) and drives radioresistance. Targeting TRAF4 may enhance radiosensitivity in NPC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Nasopharyngeal carcinoma (NPC) recurrence after radiotherapy necessitates identifying resistance factors.
- Tumor necrosis factor receptor-associated factor 4 (TRAF4) is a potential therapeutic target.
Purpose of the Study:
- To investigate the role of TRAF4 in NPC radiosensitivity.
- To elucidate the molecular mechanisms underlying TRAF4-mediated radioresistance.
Main Methods:
- TRAF4 expression analysis in NPC cells and tissues.
- TRAF4 knockdown experiments in vitro and in vivo.
- Western blot analysis of the Akt/Wee1/CDK1/survivin axis.
Main Results:
- TRAF4 is overexpressed in NPC and correlates with p-Akt and survivin.
- TRAF4 knockdown enhances NPC radiosensitivity by inhibiting the Akt/Wee1/CDK1 axis.
- TRAF4 knockdown suppresses survivin phosphorylation and promotes its degradation.
- TRAF4 knockdown overcomes radioresistance in vitro and in xenograft models.
Conclusions:
- The TRAF4-survivin axis is crucial for NPC radioresistance.
- Targeting TRAF4 represents a promising strategy for radiosensitization in NPC treatment.
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