Fusobacterium and colorectal cancer

Hai Hu1, 2*, Ziwei Zhou1, 2, Jiewen Chen2

1
Oncology Department, Sun Yat-Sen Memorial Hospital, China, 2Breast Tumor Center, Sun
Yat-Sen Memorial Hospital, China
Submitted to Journal:
Frontiers in Oncology

Specialty Section:
Gastrointestinal Cancers

ISSN:
2234-943X

Article type:

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Review Article

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Received on:

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06 Mar 2018

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Accepted on:
21 Aug 2018

r o vi Provisional PDF published on:

21 Aug 2018

Frontiers website link:

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www.frontiersin.org

Citation:
Hu H, Zhou Z and Chen J(2018) Fusobacterium and colorectal cancer. Front. Oncol. 8:371.
doi:10.3389/fonc.2018.00371

Copyright statement:
© 2018 Hu, Zhou and Chen. This is an open-access article distributed under the terms of the Creative
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 Fusobacterium and colorectal cancer
1 2 1 1*
Ziwei Zhou , Jiewen Chen , Herui Yao , Hai Hu
1
Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People’s Republic of China, Email:
zhouzw6@mail2.sysu.edu.cn

2
Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People’s Republic of China. Email:
chenjw223@mail2.sysu.edu.cn

Correspondence: Hai Hu, ,E-mail: huhai@mail.sysu.edu.cn and Herui Yao yaoherui@163.com

Colorectal cancer (CRC) is the third most common cancer worldwide and its pathogenesis has been
extensively explored over the past decades. Recently, microorganisms in the gastrointestinal tract have
emerged as potential etiological agents. In particular, a direct proportional association between
Fusobacterium and CRC has been described. Since then, the functional impact of Fusobacterium in
CRC development has been studied using various mouse models. Although some epidemiologic studies
did not establish an obvious relationship between Fusobacterium and CRC, numerous pathogenic
mechanisms leading to the disease have been described. For instance, Fusobacterium can activate the
E-cadherin/β-catenin signaling pathway and is associated with particular epigenetic phenotype, such as
microsatellite instability (MSI) and hypermethylation, via its strong adhesive and invasive abilities
resulting in malignant transformation of epithelial cells. Also, Fusobacterium could alter the tumor
microenvironment (TME) significantly by myeloid-derived suppressor cells (MDSCs), tumor
associated macrophages (TAMs), and tumor associated neutrophils (TANs) recruitment and local

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immune suppression. Herein, we provide an in-depth review of the relationship between

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Fusobacterium and colorectal cancer. In light of the emergence of microbiome-based therapeutics,

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potential therapies and preventive strategies for colorectal cancer related to Fusobacterium are also
discussed.

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Key words: Fusobacterium, colorectal cancer, tumor microenvironment, epigenetic changes, tumor immunity

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Introduction
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1. The biological features of Fusobacterium
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TABLE 1 | Studies with positive detection of Fusobacterium in colorectal diseases.
Authors Diseases Methods Samples

McCoy et al. (2013) adenoma qPCR, FISH Human tissues (62)

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Wong et al. (2017) adenoma qPCR Feces (63)

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Ito et al. (2015) Adenoma qPCR FFPE tissues (64)

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Castellarin et al. (2012) CRC RNA-seq, qPCR, WGS Human tissues (21)
Mima et al. (2015) CRC qPCR FFPE tissues (65)

Kostic et al. (2012)

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Tahara et al. (2014)
Wang et al. (2016)
Adenoma
CRC
CRC
CRC
and

qPCR

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ELISA, WB, qPCR
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qPCR, 16S rDNA Sequence, WAS, FISH Human tissues,
Feces
Human tissues
blood samples and feces
(14)

(33)
(66)

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Mehta et al. (2017) CRC qPCR FFPE tissues (29)

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qPCR: quantitative real-time polymerase chain reaction; FISH: Fluorescent quantitative polymerase chain reaction; RNA seq: RNA sequencing;

WAS: Whole-genome sequence; ELISA: Enzyme-linked immunosorbent assay; WB: Western blotting; FFPE: Formalin-fixed paraffin-embedded.

2. The impact of Fusobacterium in CRC microenvironment

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3. Fusobacterium induces epigenetic changes in tumor cells

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4. Potential management of Fusobacterium -associated CRC

FIGURE 1 Potential mechanism of Fusobacterium -associated CRC. Mutant epithelial cells cause local intestinal barrier impairment, which gives

Fusobacterium the opportunity for adherence and subsequent invasion into epithelial cells. Once FadA, a membrane protein of Fusobacterium,

combines with E-cadherin and is internalized by epithelial cells, the β-catenin signaling pathway is activated. Phosphorylated β-catenin would enter

the cell nucleus from cytoplasm and promote NF-ĸB genes, pro-inflammatory genes and the expression of many other oncogenes. Moreover, the
microenvironment of malignancies is anoxic and acidic, which would be more suitable for Fusobacterium reproduction compared to other bacteria.

The metabolites of aggregated Fusobacterium. Then recruit MDSCs, in turn suppressing anti-tumor immunity and promote CRC carcinogenesis.

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Future outlook and caveats

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Conclusion
Abbreviations

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Acknowledgement:

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