ANGPTL4-Mediated Promotion of Glycolysis Facilitates the Colonization of Fusobacterium nucleatum in Colorectal Cancer.
ANGPTL4-Mediated Promotion of Glycolysis Facilitates the Colonization of Fusobacterium nucleatum in Colorectal Cancer.
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ANGPTL4 介导的糖酵解促进促进具核梭杆菌在结直肠癌中的定植
DOI：
10.1158/0008-5472.can-21-2273
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发表时间：
2021-12-15
期刊：
影响因子：
11.2
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中科院分区：
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F.结直肠癌中的核质定殖受ANGPTL4介导的糖酵解调节，这表明该轴可以作为F.核质和癌症进展。结直肠癌是一个严重的全球性健康问题，越来越多的证据支持具核梭杆菌（F。nucleatum）与结直肠癌发展、转移和化学抗性的关系。然而，F.结直肠癌组织中的核仁尚未阐明。在这里，我们证明了F。核质感染介导的血管生成素样4（ANGPTL4）表达升高。上调的ANGPTL4在体外和体内促进结直肠癌细胞的葡萄糖摄取和糖酵解活性，这是F.核质此外，在F. nucleatum感染的结直肠癌细胞和患者肿瘤，其负责ANGPTL4的相应转录上调。这些数据表明F. nucleatum是大肠癌中F.核相关的结直肠癌。显著性：F.结直肠癌中的核质定殖受ANGPTL4介导的糖酵解调节，这表明该轴可以作为F.核质和癌症进展。图形摘要
F. nucleatum colonization in colorectal cancer is regulated by ANGPTL4-mediated glycolysis, suggesting that this axis could be targeted for combined repression of F. nucleatum and cancer progression. Colorectal cancer is a severe health problem worldwide, and accumulating evidence supports the contribution of Fusobacterium nucleatum (F. nucleatum) to colorectal cancer development, metastasis, and chemoresistance. However, the mechanisms underlying the colonization of F. nucleatum in colorectal cancer tissue are not yet clarified. Here we demonstrate that F. nucleatum infection mediated elevation of angiopoietin-like 4 (ANGPTL4) expression. Upregulated ANGPTL4 promoted glucose uptake and glycolysis activity in colorectal cancer cells in vitro and in vivo, which are necessary for the colonization of F. nucleatum. Furthermore, overall increased acetylation of histone H3 lysine 27 was observed in F. nucleatum–infected colorectal cancer cells and patient tumors, which was responsible for the corresponding transcriptional upregulation of ANGPTL4. These data indicate that the metabolic reprogramming of cancer cells induced by F. nucleatum is essential for its enrichment and persistence in colorectal cancer, providing a novel potential target for the clinical intervention of F. nucleatum–related colorectal cancer. Significance: F. nucleatum colonization in colorectal cancer is regulated by ANGPTL4-mediated glycolysis, suggesting that this axis could be targeted for combined repression of F. nucleatum and cancer progression. Graphical Abstract