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

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2016 Aug 12

PMID 27512904

Citations 381

Authors

Jawad Abed

Johanna E M Emgard

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

Affiliations

Soon will be listed here.

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.

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