Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway

Nomoto, Daichi; Baba, Yoshifumi; Liu, Yang; Tsutsuki, Hiroyasu; Okadome, Kazuo; Harada, Kazuto; Ishimoto, Takatsugu; Iwatsuki, Masaaki; Iwagami, Shiro; Miyamoto, Yuji; Yoshida, Naoya; Watanabe, Masayuki; Moroishi, Toshiro; Komohara, Yoshihiro; Sawa, Tomohiro; Baba, Hideo

doi:10.1016/j.canlet.2022.01.014

Cited by 43 publications

(27 citation statements)

References 40 publications

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“…Fusobacterium nucleatum (F. nucleatum) found in the oral cavity is associated with poor prognosis in patients with ESCC. It has been reported that F. nucleatum activated the NF- κ B pathway via the NOD1/RIPK2 pathway to promote tumor growth [ 25 ].…”

Section: Nod1 and Nod2 In Cancermentioning

confidence: 99%

NOD1 and NOD2 Are Potential Therapeutic Targets for Cancer Immunotherapy

Wang

2022

Computational Intelligence and Neuroscience

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The nucleotide oligomerization domain (NOD)-like receptors (NLRs) are a group of intracellular proteins that are essential for controlling the host's innate immune response. The cytosolic nucleotide binding oligomerization domains 1 and 2 receptors (NOD1 and NOD2) are the most widely investigated NLRs. As pattern recognition receptors (PRRs), NOD1 and NOD2 may recognize and bind endogenous damage associated molecular patterns (DAMPs) and external pathogenic associated molecular patterns (PAMPs), directing the activation of inflammatory caspases through engaging the adaptor protein RIP2, which further activates the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, thereby mediating host innate immunity and regulating the adaptive immunity. Previous research has identified NOD1 and NOD2 as key players in inflammatory disease and host-microbial defense. Despite numerous studies claiming that NOD1 and NOD2 are linked to tumorigenesis and tumor development, it is still unclear whether NOD1 and NOD2 act as cancer's friends or foes. In this review, we focus on concluding the current research progress on the role of NOD1 and NOD2 in a variety of cancers and discussing the potential reasons for the contradicting role of NOD1 and NOD2 in cancers. This review may help better understand the role of NOD1 and NOD2 in cancer and shed light on NOD1 and NOD2 as potential therapeutic targets for tumor immunotherapy.

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Section: Nod1 and Nod2 In Cancermentioning

confidence: 99%

NOD1 and NOD2 Are Potential Therapeutic Targets for Cancer Immunotherapy

Wang

2022

Computational Intelligence and Neuroscience

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“…14,[26][27][28] For example, F. nucleatum was able to enhance OSCC cell migration via integrin alpha V and FAK activation and promote ESCC progression via the NOD1/RIPK2/NF-κB pathway. 29,30 F. nucleatum is one of the most prevalent oral bacteria in biofilms from periodontal disease and has strong co-aggregation properties to help other bacteria cross the host epithelial and endothelial barrier. 31 Several F. nucleatum virulence proteins, including Fap2, FadA and lipopolysaccharide, have been proven to invade human epithelial cells, activate β-catenin signaling, induce oncogenic gene expression and promote growth of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma

Zhu

Yip

Cheung

et al. 2023

Intl Journal of Cancer

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The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case‐control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3‐V4 amplicon sequencing. Compared with their respective non‐SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC‐associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host‐microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies.

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“…Interestingly, as a cytoplasmic pattern recognition receptor, NOD1 was initially identified as a cancer-promoting factor and might cause tumor recurrence and metastasis, resulting in a poorer prognosis through pyroptosis ( Fernández-García et al, 2022 ; Nomoto et al, 2022 ). However, in our research, NOD1 showed a significant cancer suppressive effect and acted as a protective factor against AML.…”

Section: Discussionmentioning

confidence: 99%

The pyroptosis-related gene signature predicts prognosis and reveals characterization of the tumor immune microenvironment in acute myeloid leukemia

Zhou

Qian

et al. 2022

Front. Pharmacol.

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Background: Pyroptosis is a novel inflammatory form of programmed cell death and a prospective target for cancer therapy. Nevertheless, little is known about the association between pyroptosis-related genes (PRGs) and acute myeloid leukemia (AML) prognosis. Herein, we systematically investigated the specific functions and clinical prognostic value of multiple PRGs in AML.Methods: Univariate and LASSO Cox regression analyses based on TCGA and GTEx databases were used to generate the PRG signature, whose predictive efficacy of survival was evaluated using survival analysis, ROC, univariate and multivariate Cox analyses as well as subgroup analysis. The BeatAML cohort was used for data validation. The association between risk score and immune cell infiltration, HLA, immune checkpoints, cancer stem cell (CSC), tumor mutation burden (TMB), and therapeutic drug sensitivity were also analyzed.Results: Six -PRG signatures, namely, CASP3, ELANE, GSDMA, NOD1, PYCARD, and VDR were generated. The high-risk score represented a poorer prognosis and the PRG risk score was also validated as an independent predictor of prognosis. A nomogram including the cytogenetic risk, age, and risk score was constructed for accurate prediction of 1-, 3-, and 5-year survival probabilities. Meanwhile, this risk score was significantly associated with the tumor immune microenvironment (TIME). A high-risk score is characterized by high immune cell infiltration, HLA, and immune checkpoints, as well as low CSC and TMB. In addition, patients with low-risk scores presented significantly lower IC50 values for ATRA, cytarabine, midostaurin, doxorubicin, and etoposide.Conclusion: Our findings might contribute to further understanding of PRGs in the prognosis and development of AML and provide novel and reliable biomarkers for its precise prevention and treatment.

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Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway

Cited by 43 publications

References 40 publications

NOD1 and NOD2 Are Potential Therapeutic Targets for Cancer Immunotherapy

NOD1 and NOD2 Are Potential Therapeutic Targets for Cancer Immunotherapy

Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma

The pyroptosis-related gene signature predicts prognosis and reveals characterization of the tumor immune microenvironment in acute myeloid leukemia

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