<i>Fusobacterium nucleatum</i> promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis

Abstract

Metastasis is the leading cause of death for colorectal cancer (CRC) patients, and the spreading tumor cells adhesion to endothelial cells is a critical step for extravasation and further distant metastasis. Previous studies have documented the important roles of gut microbiota-host interactions in the CRC malignancy, and <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) was reported to increase proliferation and invasive activities of CRC cells. However, the potential functions and underlying mechanisms of <i>F. nucleatum</i> in the interactions between CRC cells and endothelial cells and subsequent extravasation remain unclear. Here, we uncovered that <i>F. nucleatum</i> enhanced the adhesion of CRC cells to endothelial cells, promoted extravasation and metastasis by inducing ICAM1 expression. Mechanistically, we identified that <i>F. nucleatum</i> induced a new pattern recognition receptor ALPK1 to activate NF-κB pathway, resulting in the upregulation of ICAM1. Interestingly, the abundance of <i>F. nucleatum</i> in tumor tissues of CRC patients was positively associated with the expression levels of ALPK1 and ICAM1. Moreover, high expression of ALPK1 or ICAM1 was significantly associated with a shorter overall survival time of CRC patients. This study provides a new insight into the role of gut microbiota in engaging into the distant metastasis of CRC cells.