Proinflammatory and Cancer-Promoting Pathobiont Fusobacterium nucleatum Directly Targets Colorectal Cancer Stem...

Area of Science:

• Microbiology
• Oncology
• Gastroenterology

Background:

• Intestinal bacteria influence gut health, inflammation, and colorectal cancer (CRC).
• Fusobacterium nucleatum (Fn), an oral pathobiont, is increasingly linked to CRC progression and poor outcomes.
• The specific cellular targets of Fn in CRC remain largely unknown.

Purpose of the Study:

• To investigate whether Fn directly targets colorectal cancer stem cells (CR-CSCs).
• To elucidate the molecular mechanisms underlying Fn-CSC interactions.
• To explore the therapeutic potential of targeting Fn-CSC interactions.

Main Methods:

• A patient-derived CR-CSC line, enriched for CD133, was cultured as tumor spheroids.
• CR-CSCs were exposed in vitro to varying concentrations of Fn.
• Fn adherence, immune responses, and downstream signaling pathways (e.g., protein tyrosine phosphorylation, p42/44 MAP kinase activation) were analyzed.

Main Results:

• Fn demonstrated stable adherence to CR-CSCs, mediated by CEACAM-1 and Gal-GalNac interactions.
• Fn triggered innate immune responses within CR-CSCs.
• Fn activated a protein tyrosine phosphorylation cascade, including p42/44 MAP kinase, dependent on CEACAM-1.

Conclusions:

• Fusobacterium nucleatum directly interacts with and stimulates colorectal cancer stem cells.
• This interaction involves CEACAM-1 and activates signaling pathways crucial for cancer progression.
• Targeting Fn-CSC interactions may offer novel therapeutic strategies for colorectal cancer.