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<p>To elucidate the role of eukaryotic translation initiation factor 3 subunit B (EIF3B) in laryngeal squamous cell carcinoma (LSCC) progression and its regulatory mechanism. Integrated bioinformatics analysis (GEO, TCGA), immunohistochemistry (IHC), lentiviral-mediated gene knockdown/overexpression, co-immunoprecipitation (Co-IP), Western blotting (WB), and in vivo xenograft models were employed. Clinically, our findings revealed an upregulation of EIF3B expression in LSCC, with its abnormally high levels significantly correlating with poor survival outcomes among patients. Functionally, ablation of EIF3B potently inhibited cancer cell proliferation, colony formation, and migratory abilities. Mechanistically, EIF3B stabilized MAP2K2 via direct interaction with its P3 domain, inhibiting VHL-mediated ubiquitination at K169. Notably, MAP2K2 kinase activity was essential for EIF3B-driven ERK phosphorylation and downstream oncogenic signaling. Moreover, EIF3B overexpression accelerated tumor growth in xenograft models, which was rescued by MAP2K2 knockdown. In Conclusion, EIF3B promotes LSCC progression by stabilizing MAP2K2, activating the ERK/MAPK pathway, and disrupting VHL-mediated proteostasis. Targeting the EIF3B-MAP2K2 axis may offer therapeutic strategies for LSCC.</p>

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EIF3B stabilizes MAP2K2 to activate the ERK pathway and promote the progression of laryngeal squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月21日

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  • Jie Tan,
  • Xueshi Li,
  • Yuguang Wang,
  • Lin Wang,
  • Xingguo Zhao,
  • Yixu Wang,
  • Meng Cui

摘要

To elucidate the role of eukaryotic translation initiation factor 3 subunit B (EIF3B) in laryngeal squamous cell carcinoma (LSCC) progression and its regulatory mechanism. Integrated bioinformatics analysis (GEO, TCGA), immunohistochemistry (IHC), lentiviral-mediated gene knockdown/overexpression, co-immunoprecipitation (Co-IP), Western blotting (WB), and in vivo xenograft models were employed. Clinically, our findings revealed an upregulation of EIF3B expression in LSCC, with its abnormally high levels significantly correlating with poor survival outcomes among patients. Functionally, ablation of EIF3B potently inhibited cancer cell proliferation, colony formation, and migratory abilities. Mechanistically, EIF3B stabilized MAP2K2 via direct interaction with its P3 domain, inhibiting VHL-mediated ubiquitination at K169. Notably, MAP2K2 kinase activity was essential for EIF3B-driven ERK phosphorylation and downstream oncogenic signaling. Moreover, EIF3B overexpression accelerated tumor growth in xenograft models, which was rescued by MAP2K2 knockdown. In Conclusion, EIF3B promotes LSCC progression by stabilizing MAP2K2, activating the ERK/MAPK pathway, and disrupting VHL-mediated proteostasis. Targeting the EIF3B-MAP2K2 axis may offer therapeutic strategies for LSCC.