Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway
Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway
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DOI：
10.1016/j.canlet.2022.01.014
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发表时间：
2022-01-22
期刊：
影响因子：
9.7
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
--
作者：
Nomoto, Daichi;Baba, Yoshifumi;Baba, Hideo
在口腔中发现的核梭杆菌影响胃肠道癌症的进展。此外，我们之前的研究结果表明，核梭菌与食管鳞状细胞癌（ESCC）患者预后不良有关。然而，核梭菌影响侵袭性肿瘤行为的机制尚未阐明。我们进行了这项临床、体外和体内研究，以阐明核梭菌诱导ESCC进展的机制。透射电镜显示，具核梭菌侵入并占据ESCC细胞，影响其基因和蛋白的表达。对F. nucleatum处理的ESCC细胞进行综合mRNA表达和途径富集分析，发现“nf - κ B”和“nod样受体”信号通路富集。我们证实了核梭菌的存在与切除ESCC组织中nf - κ B活化之间的关系。此外，F. nucleatum处理的ESCC细胞表现出增强的生长能力，NF-kappa B激活，以及NOD1和磷酸化RIPK2的过表达。此外，在异种移植物模型中，经处理的细胞显示出肿瘤生长加速，nf - κ B活化。F. nucleatum侵袭ESCC细胞，通过NOD1/RIPK2途径诱导NF-kappa B通路，导致肿瘤进展。
Fusobacterium nucleatum, found in the oral cavity, influences the progression of gastrointestinal cancers. Addi-tionally, our previous results suggested that F. nucleatum is associated with poor patient prognosis in esophageal squamous cell carcinoma (ESCC). However, the mechanism by which F. nucleatum affects aggressive tumor behavior has yet to be elucidated. We have conducted this clinical, in vitro, and in vivo study to clarify the mechanism of ESCC progression induced by F. nucleatum. Transmission electron microscopy revealed that F. nucleatum invaded and occupied ESCC cells and impacted gene and protein expression. Comprehensive mRNA expression and pathway enrichment analyses of F. nucleatum-treated ESCC cells identified the "NF-kappa B " and "NOD-like receptor " signaling pathways as enriched. We confirmed the relationship between the presence of F. nucleatum and NF-kappa B activation in resected ESCC tissues. Furthermore, F. nucleatum-treated ESCC cells demonstrated enhanced growth ability, and NF-kappa B acti-vation, as well as overexpression of NOD1 and phosphorylated RIPK2. Furthermore, treated cells showed accelerated tumor growth, with NF-kappa B activation in xenograft models. F. nucleatum invaded ESCC cells and induced the NF-kappa B pathway through the NOD1/RIPK2 pathway, leading to tumor progression.