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

Jawad Abed, Johanna E.M. Emgård, Gideon Zamir, Mouhammad Faroja, Gideon Almogy, Amalie Grenov, Asaf Sol, Ronit Naor, Eli Pikarsky, Karine A. Atlan, Anna Mellul, Stella Chaushu, Abigail L. Manson, Ashlee M. Earl, Nora Ou, Caitlin A. Brennan, Wendy S. Garrett*, Gilad Bachrach

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

470 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)215-225
Number of pages11
JournalCell Host and Microbe
Volume20
Issue number2
DOIs
StatePublished - 10 Aug 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

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