Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc

By Jawad Abed, Johanna E. M. Emgård, G. Zamir, M. Faroja, G. Almogy, Amalie Grenov, Asaf Sol, R. Naor, E. Pikarsky, Karine A. Atlan and 8 more. Cell Host and Microbe, 2016

770 citations recorded by the source corpus.

SUMMARY 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-Gal-NAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-Gal-NAc 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.

Subfields: Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/95c3ad3cfe72b6799297f0bf93328a5e65beb526

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In Molecular Biology

1. W. Zou
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In Surgery

1. B. Goodman
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Citations in the corpus

• The microbiome and human cancer (2021, background): “hematogenous spread (117, 172, 173) or colonized micrometastases (19) may”
• The Human Gut Microbiome – A Potential Controller of Wellness and Disease (2018, neutral): “nucleatum invasion and colonization of CRC cells (Abed et al., 2016).”
• The microbiome and cancer (2018, background): “Notwithstanding the immaturity in the field, it seems clear that different organisms can be found in both metastatic and primary cancer sites, possibly as a consequence of haematogenous [33] and local spread from a variety of sources, including the oral plaque microbiome [34], and these organisms ma”
• Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy (2017, background): “In addition, F. nucleatum lectin Fap2 may recognize the host Gal-GalNAc and help this bacterium localize abundantly in colon cancer epithelial cells (Abed et al., 2016).”