ANGPTL4-Mediated Promotion of Glycolysis Facilitates the Colonization of <i>Fusobacterium nucleatum</i> in Colorectal Cancer.

Abstract

Colorectal cancer is a severe health problem worldwide, and accumulating evidence supports the contribution of <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) to colorectal cancer development, metastasis, and chemoresistance. However, the mechanisms underlying the colonization of <i>F. nucleatum</i> in colorectal cancer tissue are not yet clarified. Here we demonstrate that <i>F. nucleatum</i> infection mediated elevation of angiopoietin-like 4 (ANGPTL4) expression. Upregulated ANGPTL4 promoted glucose uptake and glycolysis activity in colorectal cancer cells <i>in vitro</i> and <i>in vivo</i>, which are necessary for the colonization of <i>F. nucleatum</i>. Furthermore, overall increased acetylation of histone H3 lysine 27 was observed in <i>F. nucleatum</i>-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 <i>F. nucleatum</i> is essential for its enrichment and persistence in colorectal cancer, providing a novel potential target for the clinical intervention of <i>F. nucleatum</i>-related colorectal cancer. SIGNIFICANCE: <i>F. nucleatum</i> colonization in colorectal cancer is regulated by ANGPTL4-mediated glycolysis, suggesting that this axis could be targeted for combined repression of <i>F. nucleatum</i> and cancer progression.