What is the role of NF-κB signaling in Fusobacterium-associated cancer risk?

• A. It is not involved
• B. It suppresses tumor growth
• C. It promotes inflammatory signaling that may contribute to tumorigenesis
• D. It exclusively drives antiviral responses

Answer: (C)

NF-κB signaling acts as a major driver of inflammatory pathways that can fuel cancer development in the setting of Fusobacterium infection. Fusobacterium nucleatum can activate NF-κB in colonic epithelial and immune cells through microbial pattern-recognition receptors and its adhesin FadA, which engages E-cadherin and links to NF-κB and other pro-survival pathways. This activation leads to production of pro-inflammatory cytokines like IL-6 and IL-8, chemokines, and anti-apoptotic genes. The resulting chronic inflammation creates a tumor-promoting environment by increasing cell proliferation, reducing apoptosis of damaged cells, promoting genomic instability, and shaping immune cell recruitment and activation. While NF-κB also has roles in antiviral responses, in Fusobacterium-associated cancer risk it predominantly drives inflammatory signaling that can contribute to tumorigenesis.