A Positive Feed-Forward Loop Between Fusobacterium nucleatum and Ethanol Metabolism Reprogramming Drives Laryngeal Cancer Progression and Metastasis

Alcohol consumption, which affects the structure and composition of the laryngeal microbiota, is one of the most important risk factors for laryngeal squamous cell cancer (LSCC). Our results demonstrated that Fusobacterium nucleatum (F. nucleatum) highly enriched in LSCC was associated with poor prognosis. F. nucleatum increased miR-155-5p and miR-205-5p expression to suppress alcohol dehydrogenase 1B and transforming growth factor beta receptor 2 expression by activating TLR4- and MYD88-dependent innate immune signaling, resulting in ethanol metabolism reprogramming to accumulate F. nucleatum and PI3K/AKT signaling pathway activation to promote epithelial-mesenchymal transition in LSCC, further promoting uncontrolled LSCC progression and metastasis. Therefore, the positive feed-forward loop between F. nucleatum and ethanol metabolism reprogramming promotes cell proliferation, migration, and invasion to affect LSCC patient prognosis. The amount of F. nucleatum is a potential prognostic biomarker, a finding yielding valuable insight into clinical management and may potentially improving the oncologic outcome of LSCC patients.