Fusobacterium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/β-Catenin Signaling via its FadA Adhesin Original paper
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Microbes
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains key microbe types—bacteria, viruses, fungi, protozoa, and archaea—plus major pathogenic and beneficial examples.
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
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Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study explored the mechanism by which Fusobacterium nucleatum (Fn) promotes colorectal carcinogenesis. Specifically, it focused on the role of Fn’s FadA adhesin in modulating E-cadherin/beta-catenin signaling. The research aimed to understand how FadA binding to E-cadherin on colorectal cancer (CRC) cells influences tumor growth, inflammation, and oncogenesis. It also investigated how FadA contributes to the activation of inflammatory responses and the expression of oncogenic genes in CRC.
Who was studied?
The study involved human CRC cell lines (HCT116, DLD1, SW480, HT29), human non-cancerous cells (HEK 293), and xenograft mouse models. Researchers assessed the proliferation of CRC cells in response to Fn infection and the effects of FadA on these cells. Clinical specimens from patients with adenomas and adenocarcinomas were also analyzed for fadA gene expression and Fn colonization.
What were the most important findings?
The study revealed that the FadA adhesin from Fusobacterium nucleatum binds to E-cadherin on CRC cells, activating beta-catenin signaling and stimulating the growth of CRC cells. This binding leads to enhanced expression of oncogenes such as Myc and cyclin D1, as well as inflammatory cytokines like IL-6, IL-8, and IL-18. Additionally, FadA-induced tumor growth in xenograft models was shown to be dependent on E-cadherin. Importantly, FadA’s binding to E-cadherin activated both tumor-promoting Wnt signaling and inflammatory responses. These effects were modulated by clathrin-mediated endocytosis, indicating that FadA’s internalization plays a critical role in inflammation, whereas tumor growth stimulation was independent of this process. The study also demonstrated that FadA expression was significantly higher in CRC tissues compared to normal tissues, with a stepwise increase in fadA gene copies observed from normal tissues to adenomas and adenocarcinomas, supporting the bacterium’s role in CRC progression.
What are the greatest implications of this study?
The findings from this study highlight the oncogenic potential of Fusobacterium nucleatum, specifically through its FadA adhesin. By elucidating the mechanism of FadA-mediated tumor progression via E-cadherin and beta-catenin signaling, this research provides a foundation for the development of targeted therapies aimed at disrupting this interaction. In particular, the identification of an inhibitory peptide derived from the EC5 domain of E-cadherin that blocks Fn binding and invasion suggests potential for therapeutic intervention. Furthermore, the study’s discovery that elevated FadA levels correlate with CRC progression indicates that measuring fadA gene expression could serve as a diagnostic marker for identifying patients at risk for CRC, potentially leading to early detection and more effective treatment strategies.
Fusobacterium nucleatum
Fusobacterium nucleatum is a Gram-negative, anaerobic bacterium commonly found in the oral cavity, where it plays a crucial role in the formation of biofilms. Beyond its presence in the mouth, Fn is implicated in a variety of systemic conditions, including periodontal disease, colorectal cancer, and inflammatory bowel disease. Known for its ability to coaggregate with other bacteria, Fn's pathogenic potential is magnified in dysbiotic microbial communities, making it a key player in polymicrobial infections. The bacterium utilizes multiple virulence factors such as FadA and Fap2, which facilitate adhesion to host tissues and immune evasion, ultimately contributing to its role in chronic and inflammatory diseases.