Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc 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
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Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
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 examined the role of Fusobacterium nucleatum (Fn) in colorectal cancer (CRC) and its enrichment in colorectal adenocarcinomas. Specifically, it investigated the molecular mechanisms that allow Fusobacterium to localize to CRC tissues, identifying the interaction between the host polysaccharide Gal-GalNAc, overexpressed in CRC, and the fusobacterial lectin Fap2 as a key factor in this process.
Who was studied?
The study focused on human CRC tissue samples, including adenocarcinomas and adenomas, as well as murine models of CRC. Researchers analyzed the expression levels of Gal-GalNAc in CRC and its correlation with F. nucleatum colonization. Additionally, the study involved bacterial strains of F. nucleatum, including wild-type and Fap2-deficient mutants, to investigate their binding to CRC cells.
What were the most important findings?
The study revealed that F. nucleatum binds to the carbohydrate moiety Gal-GalNAc, which is overexpressed in CRC tissues. This binding is mediated by the Fusobacterium lectin Fap2, which was shown to facilitate the bacterium’s enrichment in CRC tumors. In vitro experiments demonstrated that F. nucleatum strains, particularly those expressing Fap2, preferentially adhered to CRC cell lines that exhibited high levels of Gal-GalNAc. Furthermore, the study found that intravenous injection of F. nucleatum into mice led to the localization of the bacterium to tumors in a Fap2-dependent manner, confirming the role of Fap2 in tumor colonization. In contrast, Fap2-deficient mutants showed reduced binding to CRC tissues and less tumor enrichment, suggesting that targeting Fap2 or the host Gal-GalNAc could limit the potentiation of CRC by F. nucleatum.
What are the greatest implications of this study?
The findings provide critical insights into how F. nucleatum selectively colonizes CRC tissues, primarily through its interaction with Gal-GalNAc via the Fap2 lectin. This discovery opens up new potential therapeutic strategies, including the development of inhibitors targeting the Fap2-Gal-GalNAc interaction. By disrupting this binding, it may be possible to reduce F. nucleatum’s enrichment in CRC tumors, thereby mitigating its contribution to tumor progression and improving CRC treatment outcomes. Additionally, this mechanism could serve as a diagnostic tool to identify patients with high levels of Fusobacterium colonization, particularly in relation to CRC metastasis, providing a pathway for personalized treatment approaches.
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.