title: Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin.
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.
authors: Department of Periodontics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Mara Roxana
authors: MR
authors: Rubinstein
authors: Department of Periodontics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Xiaowei
authors: X
authors: Wang
authors: Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Wendy
authors: W
authors: Liu
authors: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.|Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Yujun
authors: Y
authors: Hao
authors: School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Guifang
authors: G
authors: Cai
authors: Department of Periodontics, Case Western Reserve University, Cleveland, Ohio 44106, USA.|Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.|Department of Reproductive Biology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Yiping W
authors: YW
authors: Han
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000378:metabolism*; D063646:Carcinogenesis; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000382:microbiology* / Q000473:pathology; D016967:Fusobacterium nucleatum / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D015398:Signal Transduction; D037521:Virulence Factors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D014408:Biomarkers, Tumor; D015820:Cadherins; D037521:Virulence Factors; D051176:beta Catenin
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