ANGPTL4-Mediated Promotion of Glycolysis Facilitates the Colonization of Fusobacterium nucleatum in Colorectal Cancer

Colorectal cancer is a severe health problem worldwide, and accumulating evidence supports the contribution of Fusobacterium nucleatum (F. nucleaturn) 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 ANGPTIA. These data indicate that the metabolic reprogramming of cancer cells induced by F. nucleaturn is essential for its enrichment and persistence in colorectal cancer, providing a novel potential target for the clinical intervention of F. nudeatunirelated 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.

Automated summary

The study reveals that F. nucleatum infection leads to increased expression of ANGPTL4 in colorectal cancer cells, promoting glucose uptake and glycolysis activity essential for colonization. Furthermore, increased acetylation of histone H3 lysine 27 is observed in F. nucleatum-infected cells and patient tumors, contributing to the transcriptional upregulation of ANGPTIA. This metabolic reprogramming induced by F. nucleaturn is crucial for its persistence in colorectal cancer and may serve as a potential target for clinical intervention.