Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway

Cancer Lett. 2022 Apr 1:530:59-67. doi: 10.1016/j.canlet.2022.01.014. Epub 2022 Jan 14.


Fusobacterium nucleatum, found in the oral cavity, influences the progression of gastrointestinal cancers. Additionally, our previous results suggested that F. nucleatum is associated with poor patient prognosis in esophageal squamous cell carcinoma (ESCC). However, the mechanism by which F. nucleatum affects aggressive tumor behavior has yet to be elucidated. We have conducted this clinical, in vitro, and in vivo study to clarify the mechanism of ESCC progression induced by F. nucleatum. Transmission electron microscopy revealed that F. nucleatum invaded and occupied ESCC cells and impacted gene and protein expression. Comprehensive mRNA expression and pathway enrichment analyses of F. nucleatum-treated ESCC cells identified the "NF-κB" and "NOD-like receptor" signaling pathways as enriched. We confirmed the relationship between the presence of F. nucleatum and NF-κB activation in resected ESCC tissues. Furthermore, F. nucleatum-treated ESCC cells demonstrated enhanced growth ability, and NF-κB activation, as well as overexpression of NOD1 and phosphorylated RIPK2. Furthermore, treated cells showed accelerated tumor growth, with NF-κB activation in xenograft models. F. nucleatum invaded ESCC cells and induced the NF-κB pathway through the NOD1/RIPK2 pathway, leading to tumor progression.

Keywords: Esophageal cancer; Fusobacterium nucleatum; NF-κB; NOD1; RIPK2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Progression
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / microbiology*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / microbiology*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Fusobacterium Infections / metabolism*
  • Fusobacterium nucleatum / pathogenicity*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-kappa B / metabolism*
  • Nod1 Signaling Adaptor Protein / metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism*
  • Signal Transduction / physiology


  • NF-kappa B
  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • RIPK2 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2