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.
Bibliographical noteFunding Information:
We thank Professor Lawrence A. Tabak for useful discussions, Professor Norman Grover for valuable assistance in statistics, and Carey Ann Gallini for proofreading. This work was supported by the Israel Cancer Research Fund Project grant and Israel Science Foundation grant 201/15 to G.B. and grant RO1 CA154426 and a Hoffman-LaRoche research grant to W.S.G. W.S.G. is a SAB member of Evelo Therapeutics and Synlogic, has received research funds from Hoffman-LaRoche, and consults for Janssen Pharmaceuticals.
© 2016 Elsevier Inc.