Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating the NF-κB-MMP-2/MMP-9 signaling pathway.

BACKGROUND

Fusobacterium nucleatum (Fn) infection is implicated in colorectal cancer (CRC) progression, while the exact mechanism remains incompletely understood. This study aimed to investigate the potential involvement of Fn in CRC progression and its association with nuclear factor kappa B (NF-κB)-matrix metalloproteinase-2 (MMP-2)/matrix metalloproteinase-9 (MMP-9) signaling pathways.

METHODS

Polymerase chain reaction (PCR) was used to assess the abundance of Fn in CRC tissue and healthy controls. The correlation between Fn abundance, CRC stage, and metastasis was also investigated. In vitro experiments were conducted using two CRC cell lines, DLD-1 and SW480. The effects of Fn on invasion and migration were assessed using Transwell assays and scratch wound-healing assays. Western blotting was performed to evaluate the protein levels of MMP-2, MMP-9, and phosphorylated NF-κB.

RESULTS

The abundance of Fn in CRC tissue was closely associated with tumor (T) stage, lymph node metastasis, and distant metastasis. Fn infection was associated with increased proliferation, invasion, and migration of CRC cell lines. Increased MMP-2 and MMP-9 expression was observed following Fn infection, accompanied by elevated NF-κB phosphorylation. Inhibition of NF-κB phosphorylation mitigated the NF-κB-mediated upregulation of MMP-2 and MMP-9 levels and suppressed MMP-dependent cell proliferation, invasion, and migration.

CONCLUSIONS

Fn abundance in CRC tissue correlates with CRC T stage and lymph node metastasis. Fn promotes CRC cell proliferation, invasion, and migration, potentially through induction of MMP-2 and MMP-9 via activation of the NF-κB pathway. Targeting the Fn-NF-κB-MMPs pathway could represent a novel therapeutic strategy for preventing CRC metastasis. Additionally, Fn abundance may serve as a potential biomarker for CRC diagnosis or prognosis.