Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc
Open accessAbstract
Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic tumor formation in preclinical models. However, fusobacteria are core members of the human oral microbiome and less prevalent in the healthy gut, raising questions about how fusobacteria localize to CRC. We identify a host polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells and established CRCs in mice. Additionally, intravenously injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus, targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria potentiation of CRC.
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Metagenome analysis revealed a significant difference between the gut microbial composition of cancer patients and healthy individuals.
“Metagenome analysis revealed a significant difference between the gut microbial composition of cancer patients and healthy individuals.”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [7]
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- Authors
- Abed, J., Emgård, J. E. M., Zamir, G., Faroja, M., Almogy, G., Grenov, A., Sol, A., Naor, R., Pikarsky, E., Atlan, K. A., Mellul, A., Chaushu, S., Manson, A. L., Earl, A. M., Ou, N., Brennan, C. A., Garrett, W. S., & Bachrach, G.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Hadassah Medical Center (IL)
- Broad Institute (US)
- Harvard University (US)
- Corresponding author
- Garrett, Wendy S.
- Bachrach, Gilad
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 20
- Issue
- 2
- Pages
- 215-225
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC5465824
- OpenAlex
- W2508695471
- Cited by
- 888
- References
- 49
- Citations by year
- 2026: 112 · 2025: 155 · 2024: 109 · 2023: 117 · 2022: 112 · 2021: 81 · 2020: 69 · 2019: 48 · 2018: 45 · 2017: 33 · 2016: 5
- FWCI
- 22.56
- 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
- Israel Cancer Research Fund
- Israel Science Foundation
- National Cancer Institute (R01CA154426)
- National Institute of Allergy and Infectious Diseases (U19AI110818, K08AI078942)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- Fusobacterium nucleatum, colorectal adenocarcinoma, bacterial lectins, O-glycosylation, tumor microenvironment, hematogenous spread, oral microbiota, therapeutic targeting
- MeSH terms
- Adenocarcinoma, Animals, Bacterial Adhesion, Colonic Neoplasms, Disease Models, Animal, Epithelial Cells, Humans, Mice, Inbred BALB C, Models, Biological, Protein Binding, Antigens, Tumor-Associated, Carbohydrate, Fusobacterium nucleatum, Adhesins, Bacterial, Lectins, Cell Line, Tumor, Host-Pathogen Interactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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