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

By M. Rubinstein, Xiaowei Wang, Wendy Liu, Yujun Hao, G. Cai, Yiping W Han. Cell Host and Microbe, 2013

2,259 citations recorded by the source corpus.

SUMMARY 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. FadA levels in the colon tissue from patients with adenomas and adenocarcinomas is >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.

Subfields: Infectious Diseases, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/d53aae3623bd758ddbd977b704c08a475574529c

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In Infectious Diseases

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In Molecular Biology

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Citations in the corpus

• Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “A common denominator for these bacteria is their presence in tightly adherent fraction of bacteria capable of direct interaction with the surface of the tumor, either because of special ligandreceptor mode of adhesion (Rubinstein et al., 2013; Yu et al., 2017), ability to form biofilms and initiate ”
• Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc (2016, methodology): “F. nucleatum accelerates CRC in preclinical models using both in vitro and in vivo systems (Kostic et al., 2013; Rubinstein et al., 2013).”
• Periodontitis: from microbial immune subversion to systemic inflammation (2014, background): “Fusobacterium nucleatum is associated with colorectal cancer 158 , which has been attributed to its ability to stimulate the growth of colorectal cancer cells 159 .”
• Role of the Microbiota in Immunity and inflammation (2014, background): “Bacteria of the phylum Fusobacteria are also found at a high frequency residing within the tumor tissue and are important in inducing the traffic of tumor-promoting myeloid cells (Kostic et al., 2012, 2013; Rubinstein et al., 2013).”
• The human microbiome (2017, background): “These findings are supported by a second study that identified a highly conserved Fusobacterium nucleatum virulence factor, adhesion FadA, as an inducer of oncogenic and inflammatory responses that promote cancer cell growth [23].”