<i>Fusobacterium nucleatum</i>
            promotes colorectal cancer by inducing Wnt/β‐catenin modulator Annexin A1

Rubinstein, Mara Roxana; Baik, Jung Eun; Lagana, Stephen M.; Han, Richard P; Raab, William J.; Sahoo, Debashis; Dalerba, Piero; Wang, Yichen; Han, Yiping W.

doi:10.15252/embr.201847638

Cited by 339 publications

(277 citation statements)

References 44 publications

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“…By quantitative PCR analysis, high prevalence of F. nucleatum sequences in tumour vs. normal tissue was detected and correlated with lymph node metastasis [202]. It has been hypothesized that these F. nucleatum sequences promote carcinogenesis by stimulating the Wnt signalling cascade in CRC [203,204]. The correlation between abdominal infections and increased risk of CRC development reinforces the clinical correlation between dysbiosis and carcinogenesis.…”

Section: Cancermentioning

confidence: 87%

The mutual interplay of gut microbiota, diet and human disease

2020

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The intestinal milieu harbours the gut microbiota, consisting of a complex community of bacteria, archaea, fungi, viruses and protozoans that bring to the host organism an endowment of cells and genes more numerous than its own. In the last 10 years, mounting evidence has highlighted the prominent influence of the gut mutualistic bacterial communities on human health. Microbial colonization occurs alongside with immune system development and plays a role in intestinal physiology. The community of the gut microbiota does not undergo significant fluctuations throughout adult life. However, bacterial infections, antibiotic treatment, lifestyle, surgery and diet might profoundly affect it. Gut microbiota dysbiosis, defined as marked alterations in the amount and function of the intestinal microorganisms, is correlated with the aetiology of chronic noncommunicable diseases, ranging from cardiovascular, neurologic, respiratory and metabolic illnesses to cancer. In this review, we focus on the interplay among gut microbiota, diet and host to provide a perspective on the role of microbiota and their unique metabolites in the pathogenesis and/or progression of various human disorders. We discuss interventions based on microbiome studies, that is faecal microbiota transplantation, probiotics and prebiotics, to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach towards disease treatment.

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Section: Cancermentioning

confidence: 87%

The mutual interplay of gut microbiota, diet and human disease

2020

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“…Previous studies have supported a causal effect of Fn in CRC (64,65). Binding of Fn has unique adhesin, FadA, to E-cadherin leads to activation of Wnt/β-catenin signaling, which causes overexpression of Wnt genes, oncogenes c-Myc, Cyclin D1, and inflammatory genes (64).…”

Section: Discussionmentioning

confidence: 94%

“…Binding of Fn has unique adhesin, FadA, to E-cadherin leads to activation of Wnt/β-catenin signaling, which causes overexpression of Wnt genes, oncogenes c-Myc, Cyclin D1, and inflammatory genes (64). Fn selectively promotes the growth of cancerous cells by inducing Wnt/β-catenin modulator Annexin A1 (65). Also, Fn promotes chemoresistance to CRC by modulating autophagy (18).…”

Section: Discussionmentioning

confidence: 99%

DNA glycosylase NEIL2 preventsFusobacterium-mediated inflammation and DNA damage in colonic epithelial cells

Sayed

Chakraborty

Ali

et al. 2020

Preprint

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Colorectal cancer (CRC) is the third most prevalent and deadly cancer. Approximately, 15-20 % of CRCs display microsatellite instability (MSI); however, the majority (80-85%) of cases are sporadic and known as microsatellite stable (MSS). Several recent studies indicated that infection and uncontrolled inflammation initiate DNA damage and lead to cancer progression. One of the major microbes, Fusobacterium nucleatum (Fn) is highly associated with CRC, but the role of DNA repair in microbe-associated CRC has been largely unknown. Here we show that NEIL2, an oxidized base-specific DNA glycosylase, is significantly downregulated among all the key DNA repair proteins involved in various DNA repair pathways, after infection of Fn with stemcell-based enteroid-derived monolayers (EDMs) of murine and human healthy subjects. Furthermore, following Fn infection, NEIL2-null mouse-derived EDMs showed significantly higher level of DNA damage, including double strand breaks, and inflammatory cytokines..Murine CRC model also showed downregulation of the NEIL2 transcript and accumulation of DNA damage. Importantly, analysis of publicly available transcriptomic data showed that the downregulation of NEIL2 is specific for MSS compared to MSI CRCs. We thus conclude that the pathogenic bacterial infection-induced downregulation of NEIL2, and consequent accumulation of DNA damage, play critical roles in the progression of CRC.

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“…Detection of Fusobacterium DNA using polymerase chain reaction (PCR) increases the detection sensitivity of standard fecal immunochemical test [32], indicating its potential clinical application as a noninvasive diagnostic marker. On the other hand, current evidence also suggests a role of Fusobacterium nucleatum in promoting the growth and metastasis of colorectal cancer [11,27], and the level of Fusobacterium nucleatum in the colorectal cancer-associated microbiota is correlated with poor prognosis in the patients [10,25]. Hence, Fusobacterium nucleatum can be used as a prognosis biomarker for colorectal cancer as well.…”

Section: Introductionmentioning

confidence: 99%

Fusobacterium nucleatum Promotes Gastric Cancer Aggressiveness through Upregulation of Cell Mobility and Interferon Genes

Hsieh

Tung

Pan

et al. 2020

Preprint

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Background Fusobacterium nucleatum was previously found to become a dominant species in the gastric cancer-associated microbiota of patients from Taiwan. However, the prevalence of Fusobacterium nucleatum infection in gastric cancer has not been examined in a larger patient cohort. In addition, whether Fusobacterium nucleatum elicits a cellular response in gastric cancer remains unknown.Methods A study cohort of resected gastric cancer tissue specimens was examined using nested PCR to detect Fusobacterium nucleatum. In vitro coculture of Fusobacterium nucleatum was carried out to identify the alteration in the expression profile of patient-derived gastric cancer cell line.Results approximately one-third of gastric cancer tissues are positive for Fusobacterium nucleatum. Statistical analysis showed that the risk for Fusobacterium nucleatum infection is increased in late-stage cancer tissue specimens and incurs poorer survival in Helicobacter pylori-positive patients. In vitro coculture experiment shows a drastic interferon response activated only by a high multiplicity of infection, and the response peaks within 24 hours and subsides after 72 hours of incubation. Another set of response genes is the continuous increase of actins and their regulators with prolonged time of incubation, activated by both low and high multiplicity of infection.Conclusions Our data indicates that Fusobacterium nucleatum incites an inflammatory response from the cancer cells and promotes cell mobility, likely

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Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β‐catenin modulator Annexin A1

Cited by 339 publications

References 44 publications

The mutual interplay of gut microbiota, diet and human disease

The mutual interplay of gut microbiota, diet and human disease

DNA glycosylase NEIL2 preventsFusobacterium-mediated inflammation and DNA damage in colonic epithelial cells

Fusobacterium nucleatum Promotes Gastric Cancer Aggressiveness through Upregulation of Cell Mobility and Interferon Genes

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