title: Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc.
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.
authors: The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Jawad
authors: J
authors: Abed
authors: The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Johanna E M
authors: JE
authors: Emgård
authors: Department of General Surgery, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors: Gideon
authors: G
authors: Zamir
authors: Department of General Surgery, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors: Mouhammad
authors: M
authors: Faroja
authors: Department of General Surgery, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors: Gideon
authors: G
authors: Almogy
authors: The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Amalie
authors: A
authors: Grenov
authors: The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Asaf
authors: A
authors: Sol
authors: The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Ronit
authors: R
authors: Naor
authors: Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel; Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors: Eli
authors: E
authors: Pikarsky
authors: Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors: Karine A
authors: KA
authors: Atlan
authors: Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors: Anna
authors: A
authors: Mellul
authors: Department of Orthodontics, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Stella
authors: S
authors: Chaushu
authors: Broad Institute of MIT and Harvard University, Cambridge, MA 02141, USA.
authors: Abigail L
authors: AL
authors: Manson
authors: Broad Institute of MIT and Harvard University, Cambridge, MA 02141, USA.
authors: Ashlee M
authors: AM
authors: Earl
authors: Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors: Nora
authors: N
authors: Ou
authors: Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors: Caitlin A
authors: CA
authors: Brennan
authors: Broad Institute of MIT and Harvard University, Cambridge, MA 02141, USA; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: wgarrett@hsph.harvard.edu.
authors: Wendy S
authors: WS
authors: Garrett
authors: The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel. Electronic address: giladba@ekmd.huji.ac.il.
authors: Gilad
authors: G
authors: Bachrach
mesh_terms: D000230:Adenocarcinoma / Q000382:microbiology / Q000473:pathology*; D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D001422:Bacterial Adhesion; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000382:microbiology / Q000473:pathology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D016967:Fusobacterium nucleatum / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011485:Protein Binding
chemical_list: D018829:Adhesins, Bacterial; D015295:Antigens, Tumor-Associated, Carbohydrate; D037102:Lectins; C016467:Thomsen-Friedenreich antigen