A positive feed-forward loop between Fusobacterium nucleatum and ethanol metabolism reprogramming drives laryngeal cancer progression and metastasis

Hsueh, Chi‐Yao; Huang, Qiang; Gong, Hongli; Shen, Yujie; Sun, Ji; Lau, Hui-Ching; Zhang, Duo; Tang, Di; Wu, Chunping; Guo, Yang; Huang, Huiying; Cao, Pengyu; Tao, Lei; Zhang, Ming; Zhou, Liang

doi:10.1016/j.isci.2022.103829

Cited by 15 publications

(18 citation statements)

References 48 publications

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“…Previous researches have also indicated that PI3K pathway is an important signal regulating PD-L1 expression in cancer progression [ 23 , 24 ]. And F. nucleatum treatment could activate PI3K pathway [ 25 , 26 ]. To investigate whether F. nucleatum induced PD-L1 expression also depended on activating PI3K pathway, we treated CRC cells with the PI3K inhibitor, LY294002, prior to F. nucleatum coculture.…”

Section: Resultsmentioning

confidence: 99%

Fusobacterium nucleatum stimulates cell proliferation and promotes PD-L1 expression via IFIT1-related signal in colorectal cancer

Gao

Zou

et al. 2023

Neoplasia

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Section: Resultsmentioning

confidence: 99%

Fusobacterium nucleatum stimulates cell proliferation and promotes PD-L1 expression via IFIT1-related signal in colorectal cancer

Gao

Zou

et al. 2023

Neoplasia

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“…31 The human upper aerodigestive tract harbors Fusobacterium and F. nucleatum, which are known to be associated with inflammatory diseases 32 and even lead to HNSCC. 33,34 The Fusobacterium abundance has been the focus of much investigation in the search for potential diagnostic and prognostic predictors in oral carcinomas. 35 Our results demonstrated the hypothesis that a higher Fusobacterium abundance results in a poor prognosis for HNSCC patients.…”

Section: Discussionmentioning

confidence: 99%

Fusobacterium nucleatum impairs DNA mismatch repair and stability in patients with squamous cell carcinoma of the head and neck

Hsueh

Lau

Huang

et al. 2022

Cancer

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Background Dysbiosis of the laryngeal microbiota has been demonstrated to the development of head and neck squamous cell carcinoma (HNSCC), but the association of Fusobacterium and Fusobacterium nucleatum (F. nucleatum) with DNA mismatch repair (MMR) and microsatellite instability (MSI) has not been investigated. Methods The abundance of Fusobacterium and F. nucleatum, the status of deficient MMR (dMMR) and MSI, and MMR‐related gene expression were analyzed in 171 HNSCC tissues, 61 paired para‐tumor tissues, and 60 vocal cord polyp tissues. The molecular mechanism of F. nucleatum and MMR‐related gene expression were investigated in two human HNSCC cell lines (Tu 686 and FD‐LSC‐1). Results Our results demonstrated that a high Fusobacterium abundance was detected in the HNSCC tissues and was exaggerated in the recurrent patients. We further found that a high Fusobacterium abundance was detected in the HNSCC tissues with dMMR and MSI. The Fusobacterium abundance was negatively correlated with the expression of MLH1, MSH2, and MSH6 in the HNSCC tissues. The Fusobacterium abundance was closely associated with the F. nucleatum abundance in the HNSCC tissues. F. nucleatum increased miR‐205‐5p expression to suppress MLH1, MSH2, and MSH6 expression via the TLR4‐ and MYD88‐dependent innate immune signaling pathway, resulting in dMMR, DNA damage, and cell proliferation in HNSCC. Conclusions F. nucleatum impacts HNSCC epigenetic changes in tissues with dMMR to promote DNA damage and cell proliferation by suppressing MMR‐related gene expression via the TLR4/MYD88/miR‐205‐5p signaling pathway, which is valuable in the development of efficient strategies for HNSCC prevention and treatment. LAY SUMMARY This study clearly indicates that Fusobacterium induced head and neck squamous cell carcinoma (HNSCC) aggressiveness to affect poor prognosis in HNSCC patients by epigenetic alteration of DNA mismatch repair (MMR) and microsatellite instability. Moreover, the research has shown that Fusobacterium nucleatum ( F. nucleatum ) impacts HNSCC epigenetic changes in tissues with deficient MMR to promote DNA damage and cell proliferation by suppressing MMRrelated gene expression via the TLR4/MYD88/miR‐205‐5p signaling pathway.

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“…Hsueh et al. also verified that the high abundance of F. nucleatum in laryngeal squamous cell cancer (LSCC) was associated with poor prognosis ( 64 ). In contrast, Neuzillet et al.…”

Section: F Nucleatum In Oral and Head And Neck Cancermentioning

confidence: 96%

“…A recent study showed that F. nucleatum increased the expression of miR-155-5p and miR-205-5p though MYD88-dependent TLR4 signaling, resulting in ethanol metabolism reprogramming via suppression of transforming growth factor β receptor 2 (TGFBR2) expression and subsequent suppression of alcohol dehydrogenase 1B (ADH1B) expression and promotion of EMT in LSCC. The positive feed-forward loop between F. nucleatum and ethanol metabolism reprogramming finally exacerbated the uncontrolled progression and metastasis of LSCC ( 64 ). Taken together, recent data provided preliminary evidence that EMT could be a probable link between F. nucleatum infection and the initiation of oral/head and neck epithelial carcinomas ( Figure 2 ).…”

Section: F Nucleatum In Oral and Head And Neck Cancermentioning

confidence: 99%

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Involvement of Fusobacterium nucleatum in malignancies except for colorectal cancer: A literature review

Tian

Wei

et al. 2022

Front. Immunol.

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Fusobacterium nucleatum (F. nucleatum) is originally an oral opportunistic pathogen and accumulating evidence links the presence of F. nucleatum with the pathogenicity, development, and prognosis of colorectal cancer (CRC). However, only limited preliminary data is available dealing with the role of F. nucleatum in other malignancies except for CRC. The present review aims to update and systematize the latest information about the mechanisms of F. nucleatum-mediating carcinogenesis, together with the detection rates, clinicopathological, and molecular features in F. nucleatum-associated malignancies. Comparing with adjacent non-tumorous tissue, previous studies have shown an overabundance of intratumoural F. nucleatum. Although the prognostic role of F. nucleatum is still controversial, a higher prevalence of F. nucleatum was usually associated with a more advanced tumor stage and a worse overall survival. Preliminary evidence have shown that epithelial-to-mesenchymal transition (EMT) and relevant inflammation and immune response aroused by F. nucleatum may be the probable link between F. nucleatum infection and the initiation of oral/head and neck cancer. Further studies are needed to elucidate the etiologic role of the specific microbiota and the connection between the extent of periodontitis and carcinogenesis in different tumor types. The mechanisms of how the antibiotics exerts the critical role in the carcinogenesis and antitumor effects in malignancies other than CRC need to be further explored.

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A positive feed-forward loop between Fusobacterium nucleatum and ethanol metabolism reprogramming drives laryngeal cancer progression and metastasis

Cited by 15 publications

References 48 publications

Fusobacterium nucleatum stimulates cell proliferation and promotes PD-L1 expression via IFIT1-related signal in colorectal cancer

Fusobacterium nucleatum stimulates cell proliferation and promotes PD-L1 expression via IFIT1-related signal in colorectal cancer

Fusobacterium nucleatum impairs DNA mismatch repair and stability in patients with squamous cell carcinoma of the head and neck

Involvement of Fusobacterium nucleatum in malignancies except for colorectal cancer: A literature review

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