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Cell Host Microbe. 2013 Aug 14;14(2):195-206. doi: 10.1016/j.chom.2013.07.012.

Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin.

Author information

1
Department of Periodontics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
2
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
3
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
4
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.
5
School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
6
Department of Reproductive Biology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
#
Contributed equally

Abstract

Fusobacterium nucleatum (Fn) has been associated with colorectal cancer (CRC), but causality and underlying mechanisms remain to be established. We demonstrate that Fn adheres to, invades, and induces oncogenic and inflammatory responses to stimulate growth of CRC cells through its unique FadA adhesin. FadA binds to E-cadherin, activates β-catenin signaling, and differentially regulates the inflammatory and oncogenic responses. The FadA-binding site on E-cadherin is mapped to an 11-amino-acid region. A synthetic peptide derived from this region of E-cadherin abolishes FadA-induced CRC cell growth and oncogenic and inflammatory responses. The fadA gene levels in the colon tissue from patients with adenomas and adenocarcinomas are >10-100 times higher compared to normal individuals. The increased FadA expression in CRC correlates with increased expression of oncogenic and inflammatory genes. This study unveils a mechanism by which Fn can drive CRC and identifies FadA as a potential diagnostic and therapeutic target for CRC.

PMID:
23954158
PMCID:
PMC3770529
DOI:
10.1016/j.chom.2013.07.012
[Indexed for MEDLINE]
Free PMC Article

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