Integrating Transcriptomics and Metabolomics to Explore the Novel Pathway of Fusobacterium nucleatum Invading Colon Cancer Cells

Abstract

Colorectal cancer (CRC) is a malignancy with a very high incidence and mortality rate worldwide. Fusobacterium nucleatum bacteria and their metabolites play a role in inducing and promoting CRC; however, no studies on the exchange of information between Fusobacterium nucleatum extracellular vesicles (Fnevs) and CRC cells have been reported. Our research shows that Fusobacterium nucleatum ATCC25586 secretes extracellular vesicles carrying active substances from parental bacteria which are endocytosed by colon cancer cells. Moreover, Fnevs promote the proliferation, migration, and invasion of CRC cells and inhibit apoptosis; they also improve the ability of CRC cells to resist oxidative stress and SOD enzyme activity. The genes differentially expressed after transcriptome sequencing are mostly involved in the positive regulation of tumor cell proliferation. After detecting differential metabolites using liquid chromatography-tandem mass spectrometry, Fnevs were found to promote cell proliferation by regulating amino acid biosynthesis in CRC cells and metabolic pathways such as central carbon metabolism, protein digestion, and uptake in cancer. In summary, this study not only found new evidence of the synergistic effect of pathogenic bacteria and colon cancer tumor cells, but also provides a new direction for the early diagnosis and targeted treatment of colon cancer.