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.

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ANGPTL4 介导的糖酵解促进促进结直肠癌中具核梭杆菌的定植

结直肠癌是世界范围内严重的健康问题，越来越多的证据支持具核梭杆菌 (F. nucleatum) 对结直肠癌的发展、转移和化学耐药性的贡献。然而，F. nucleatum 在结直肠癌组织中定植的潜在机制尚未阐明。在这里，我们证明 F. nucleatum 感染介导了血管生成素样 4 (ANGPTL4) 表达的升高。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，这是具核梭杆菌定植所必需的。此外，在具核梭杆菌感染的结直肠癌细胞和患者肿瘤中观察到组蛋白 H3 赖氨酸 27 的乙酰化总体增加，它负责 ANGPTL4 的相应转录上调。这些数据表明，具核梭杆菌诱导的癌细胞代谢重编程对其在结直肠癌中的富集和持久性至关重要，为具核梭杆菌相关结直肠癌的临床干预提供了一个新的潜在靶点。意义：结直肠癌中具核梭菌的定植受 ANGPTL4 介导的糖酵解调节，表明该轴可靶向联合抑制具核梭菌和癌症进展。