Format

Send to

Choose Destination
Cell Host Microbe. 2016 Aug 10;20(2):215-25. doi: 10.1016/j.chom.2016.07.006.

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

Author information

1
The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
2
Department of General Surgery, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
3
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.
4
Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
5
Department of Orthodontics, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
6
Broad Institute of MIT and Harvard University, Cambridge, MA 02141, USA.
7
Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
8
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.
9
The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel. Electronic address: giladba@ekmd.huji.ac.il.

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.

Comment in

PMID:
27512904
PMCID:
PMC5465824
DOI:
10.1016/j.chom.2016.07.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center