Effect of Fusobacterium nucleatum on proliferation, migration and epithelial-to-mesenchymal transition of colorectal cancer cells

Abstract:

[Objective] This study aims to investigate the effects of Fusobacterium nucleatum on the proliferation, adhesion, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT) of colorectal cancer cell line HCT116 and human normal colon epithelial cell line HCoEpiC. [Methods] HCT116 and HCoEpiC cells were stimulated with F. nucleatum ATCC 23726 at different multiplicity of infection (MOI) to establish infection models, and then MTT, plate cloning assay, wound healing assay, and transwell assay were employed to measure cell proliferation, migration, and invasion. Flow cytometry was employed to detect cell apoptosis. The expression levels of E-cadherin, catenin δ-1, N-cadherin, and vimentin were determined by Western blotting. [Results] F. nucleatum promoted the proliferation, induced the migration and invasion, and did not induce the apoptosis of HCT116 cells. However, it inhibited the proliferation, migration, and invasion and accelerated the apoptosis of HCoEpiC cells. F. nucleatum exhibited strong adhesion to HCT116 and HCoEpiC cells, resulting in dispersed and elongated cells and reduced intercellular adhesion. This bacterium down-regulated the expression levels of the epithelial markers E-cadherin and catenin δ-1 and up-regulated those of the mesenchymal markers N-cadherin and vimentin in HCT116 and HCoEpiC cells. In addition, it promoted the transition of E-cadherin from the cell membrane to the cytoplasm. [Conclusion] F. nucleatum can adhere to both normal colon epithelial cells and colon cancer cells and induce EMT. However, it inhibited the proliferation, migration, and invasion of human normal colon epithelial cells, showing the effect opposite to that on colon cancer cells.

Key words:Fusobacterium nucleatum;colon cancer;cell proliferation;migration;epithelial-tomesenchymal transition