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<p>Patients with metastasis have an extremely poor prognosis in head and neck squamous cell carcinoma (HNSCC). Emerging studies have illuminated the impact of intratumor microbiota on cancer metastasis, though the specific role of <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) in HNSCC metastasis remains unresolved. This research found that intratumoral <i>F. nucleatum</i> abundance was elevated and correlated to diminished disease-free survival in HNSCC patients exhibiting lymph node metastasis. <i>F. nucleatum</i> invasion into primary and metastatic tumor tissues was observed using fluorescence in situ hybridization<i>. F. nucleatum</i> induced adhesion to endothelial cells and facilitated transendothelial migration via upregulating ESPN expression in HNSCC cells, which is an actin-binding protein. Mechanistically, <i>F. nucleatum</i> activated TLR4 signaling, inducing elevated expression of the transcription factor MYB, which subsequently stimulated ESPN transcription. Furthermore, metronidazole treatment significantly reduced metastatic incidence in vivo. These results indicate the significant potential of targeting <i>F. nucleatum</i> as a therapeutic approach in metastatic HNSCC.</p>

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Fusobacterium nucleatum promotes tumor extravasation and metastasis in head and neck cancer via TLR4/MYB/ESPN axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月25日

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  • Xiaohui Yuan,
  • Huiying Huang,
  • Zhenwei Wang,
  • Hui-Ching Lau,
  • Qiang Huang,
  • Yujie Shen,
  • Ming Zhang,
  • Lei Tao,
  • Hongli Gong,
  • Chi-Yao Hsueh,
  • Liang Zhou

摘要

Patients with metastasis have an extremely poor prognosis in head and neck squamous cell carcinoma (HNSCC). Emerging studies have illuminated the impact of intratumor microbiota on cancer metastasis, though the specific role of Fusobacterium nucleatum (F. nucleatum) in HNSCC metastasis remains unresolved. This research found that intratumoral F. nucleatum abundance was elevated and correlated to diminished disease-free survival in HNSCC patients exhibiting lymph node metastasis. F. nucleatum invasion into primary and metastatic tumor tissues was observed using fluorescence in situ hybridization. F. nucleatum induced adhesion to endothelial cells and facilitated transendothelial migration via upregulating ESPN expression in HNSCC cells, which is an actin-binding protein. Mechanistically, F. nucleatum activated TLR4 signaling, inducing elevated expression of the transcription factor MYB, which subsequently stimulated ESPN transcription. Furthermore, metronidazole treatment significantly reduced metastatic incidence in vivo. These results indicate the significant potential of targeting F. nucleatum as a therapeutic approach in metastatic HNSCC.