ANGPTL4-mediated promotion of glycolysis facilitates the colonization of Fusobacterium nucleatum in colorectal cancer.

Abstract

Colorectal cancer (CRC) is a severe health problem worldwide, and accumulating evidence supports the contribution of Fusobacterium nucleatum to CRC development, metastasis, and chemoresistance. However, the mechanisms underlying the colonization of F. nucleatum in CRC tissue is 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 CRC 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 CRC 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 CRC, providing a novel potential target for the clinical intervention of F. nucleatum-related CRC.