TY - JOUR
T1 - Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc
AU - Abed, Jawad
AU - Emgård, Johanna E.M.
AU - Zamir, Gideon
AU - Faroja, Mouhammad
AU - Almogy, Gideon
AU - Grenov, Amalie
AU - Sol, Asaf
AU - Naor, Ronit
AU - Pikarsky, Eli
AU - Atlan, Karine A.
AU - Mellul, Anna
AU - Chaushu, Stella
AU - Manson, Abigail L.
AU - Earl, Ashlee M.
AU - Ou, Nora
AU - Brennan, Caitlin A.
AU - Garrett, Wendy S.
AU - Bachrach, Gilad
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/10
Y1 - 2016/8/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84991644107&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2016.07.006
DO - 10.1016/j.chom.2016.07.006
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C2 - 27512904
AN - SCOPUS:84991644107
SN - 1931-3128
VL - 20
SP - 215
EP - 225
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -
