Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation.
Camille Martin-GallausiauxLaurène SalesseDiego Garcia-WeberLudovica MarinelliFabienne Beguet-CrespelVincent BrochardCamille Le GléauAlexandre JametJoel DoreHervé M BlottièreCécile ArrieumerlouNicolas LapaquePublished in: Gut microbes (2023)
The anaerobic bacterium Fusobacterium nucleatum is significantly associated with human colorectal cancer (CRC) and is considered a significant contributor to the disease. The mechanisms underlying the promotion of intestinal tumor formation by F. nucleatum have only been partially uncovered. Here, we showed that F. nucleatum releases a metabolite into the microenvironment that strongly activates NF-κB in intestinal epithelial cells via the ALPK1/TIFA/TRAF6 pathway. Furthermore, we showed that the released molecule had the biological characteristics of ADP-heptose. We observed that F. nucleatum induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, BIRC3 and TNFAIP3 . Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity in vitro . Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in Fusobacterium induced-CRC pathogenesis, and identify the role of ADP-H in this process.
Keyphrases
- cell death
- oxidative stress
- induced apoptosis
- endothelial cells
- cell cycle arrest
- poor prognosis
- stem cells
- signaling pathway
- high glucose
- microbial community
- genome wide
- wastewater treatment
- anti inflammatory
- gene expression
- diabetic rats
- lps induced
- dna methylation
- binding protein
- risk assessment
- pi k akt
- bioinformatics analysis
- long non coding rna
- genome wide identification