Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation

Camille Martin-Gallausiaux (1) , Laurène Salesse (1) , Diego Garcia-Weber , Ludovica Marinelli (1) , Fabienne Beguet-Crespel (1) , Vincent Brochard (1) , Camille Le Gléau (1) , Alexandre Jamet (1) , Joël Doré (1) , Hervé M Blottière (1) , Cécile Arrieumerlou , Nicolas Lapaque (1)

1 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé

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 ADPheptose. 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.

Mots clés: Fusobacterium; ALPK1; colorectal cancer; NF-κB

Domaines: Médecine humaine et pathologie

Camille Martin-Gallausiaux, Laurène Salesse, Diego Garcia-Weber, Ludovica Marinelli, Fabienne Beguet-Crespel, et al.. Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation. Gut microbes, 2024, 16 (1), pp.2295384. ⟨10.1080/19490976.2023.2295384⟩. ⟨hal-04484107⟩