Fusobacterium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/β-Catenin Signaling via its FadA Adhesin
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Fusobacterium nucleatum (Fn) has been associated with colorectal cancer (CRC), but causality and underlying mechanisms remain to be established. We demonstrate that Fn adheres to, invades, and induces oncogenic and inflammatory responses to stimulate growth of CRC cells through its unique FadA adhesin. FadA binds to E-cadherin, activates β-catenin signaling, and differentially regulates the inflammatory and oncogenic responses. The FadA-binding site on E-cadherin is mapped to an 11-amino-acid region. A synthetic peptide derived from this region of E-cadherin abolishes FadA-induced CRC cell growth and oncogenic and inflammatory responses. The fadA gene levels in the colon tissue from patients with adenomas and adenocarcinomas are >10-100 times higher compared to normal individuals. The increased FadA expression in CRC correlates with increased expression of oncogenic and inflammatory genes. This study unveils a mechanism by which Fn can drive CRC and identifies FadA as a potential diagnostic and therapeutic target for CRC.
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Some members of CRC signature, such as F. nucleatum and P. anaerobius, promote colorectal carcinogenesis and modulate tumour immunity.
“Some members of this signature, such as F. nucleatum and P. anaerobius, have been shown to promote colorectal carcinogenesis and modulate tumour immunity74,75”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [74]
F. nucleatum's fadA adhesin allows it to adhere to and invade human epithelial cells, eliciting an inflammatory response and stimulating cell proliferation.
“F. nucleatum's fadA, a unique adhesin, allows it to adhere to and invade human epithelial cells, eliciting an inflammatory response97 and stimulating cell proliferation.98”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [98]
Experimental evidence implicates several microbes with virulence factors that amplify tumorigenesis through E-cadherin/Wnt/β-Catenin signaling, including FadA from Fusobacterium nucleatum and AvrA from Salmonella strains.
“Experimental evidence also implicates several microbes with virulence factors that amplify tumorigenesis via E-cadherin/Wnt/β-Catenin signaling, including FadA from Fusobacterium nucleatum and AvrA from several Salmonella strains (42, 43).”
From The microbiome and human cancer (2021) · cites this paper as [43]
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- Authors
- Rubinstein, M. R., Wang, X., Liu, W., Hao, Y., Cai, G., & Han, Y. W.
- Affiliations
- Case Western Reserve University (US)
- Case Comprehensive Cancer Center (US)
- Corresponding author
- Han, Yiping W.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 14
- Issue
- 2
- Pages
- 195-206
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3770529
- OpenAlex
- W2006292369
- Cited by
- 2,476
- References
- 51
- Citations by year
- 2026: 315 · 2025: 330 · 2024: 258 · 2023: 286 · 2022: 239 · 2021: 244 · 2020: 223 · 2019: 165 · 2018: 131 · 2017: 101 · 2016: 70 · 2015: 54 · 2014: 48 · 2013: 11
- FWCI
- 74.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Dental and Craniofacial Research (R01DE023332, R01DE014924, R01DE14924)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Fusobacterium nucleatum, colorectal cancer, E-cadherin, β-catenin signaling, colorectal carcinogenesis, bacterial adhesion, tumor invasion, inflammation, colorectal adenoma, diagnostic biomarkers, therapeutic target, synthetic peptides
- MeSH terms
- Binding Sites, Cell Line, Humans, Protein Binding, Biomarkers, Tumor, Colorectal Neoplasms, Signal Transduction, Cadherins, Fusobacterium nucleatum, Adhesins, Bacterial, Virulence Factors, beta Catenin, Carcinogenesis
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