Fusobacterium nucleatum drives gastric cancer metastasis via Gbp-CypA-NF-κB-mediated CXCL8 crosstalk between tumor cells and mast cells

作者：Xinyi Yang, Tingting Ning, Wanru Zhang, Songyuan Hou, Jiayi Su, Wenkun Li, Jing Wu · 发表于：Cell Communication and Signaling · 年份：2025 · DOI：10.1186/s12964-025-02561-w · 被引用次数：5 · 研究领域：Cancer Research and Treatments、Chemokine receptors and signaling、Helicobacter pylori-related gastroenterology studies

Gastric microbiota dysbiosis is closely linked to chronic inflammation and carcinogenesis. Fusobacterium nucleatum (Fn), an opportunistic gastrointestinal pathogen, is implicated in perturbing the immune system and form an inflammatory microenvironment that fuels the occurrence and progression of gastric cancer (GC). However, the underlying mechanisms remain elusive. We aimd to investigate the impacts of Fn on GC cells and the crosstalk between GC cells and mast cells (MCs). Fn abundance and MC infiltration were assessed in clinical GC tissues. Cell-based functional experiments, including wound healing, transwell, and ELISA, were performed using conditioned medium-based co-culture systems to explore how Fn influenced GC cell migration and the crosstalk with MC. A murine lung metastasis model was employed to evaluate Fn-driven metastasis and the effects of metronidazole and Reparixin. We showed that Fn and MCs were enriched and positively correlated in clinical GC tissues compared to paracancerous tissues. Fn and MCs exhibited tumor-promoting properties by facilitating GC cell migration. Besides, Fn and GC cells can recruit MCs and facilitate its activation. This crosstalk between GC cells and MCs was further enhanced by Fn, thereby amplifying this positive feedback loop between them. The production of CXCL8 in response to Fn stimulation was a significant mediator. Suppression of CXCL8 in GC cells weakened Fn’s promoting effects on GC cell migration, MC recruitment and activat...