Fusobacterium nucleatum interacts with cancer-associated fibroblasts to promote colorectal cancer
Gut microbial species contribute to colorectal cancer (CRC) by interacting with tumor or immune cells, however if CRC-associated bacteria engage with stromal components of the tumor microenvironment remains unclear. Here, we report interaction between the CRC-associated bacterium Fusobacterium nucleatum and cancer-associated fibroblasts (CAFs), and show that F. nucleatum is present in the stromal compartment in murine CRC models in vivo and can attach to and invade CAFs. F. nucleatum-exposed CAFs exhibit a pronounced inflammatory-CAF (iCAF) phenotype, marked by elevated expression of established iCAF markers, secretion of pro-inflammatory cytokines such as CXCL1, IL-6 and IL-8, generation of reactive oxygen species (ROS), and an increased metabolic activity. In co-culture experiments, the interaction of cancer cells with F. nucleatum-stimulated CAFs enhances invasion, a finding further validated in vivo. Altogether, our results point to a role for the tumor microbiome in CRC progression by remodeling the tumor microenvironment through its influence on cancer-associated fibroblasts, suggesting novel therapeutic strategies for targeting CRC.
Authors
- Dominik Ternes (ORCID: https://orcid.org/0000-0002-3507-6799)
- Maryse Schmoetten
- Cedric Gilson (ORCID: https://orcid.org/0000-0001-7257-1097)
- Vitaly I. Pozdeev (ORCID: https://orcid.org/0000-0002-6526-9890)
- Mohaned Benzarti (ORCID: https://orcid.org/0000-0002-6413-3983)
- Michel Mittelbronn (ORCID: https://orcid.org/0000-0002-2998-052X)
- Anaïs Carpentier (ORCID: https://orcid.org/0009-0001-6871-3301)
- Pau Pérez Escriva (ORCID: https://orcid.org/0000-0002-2330-4248)
- Mina Tsenkova (ORCID: https://orcid.org/0000-0001-9814-7921)
- Anthoula Gaigneaux (ORCID: https://orcid.org/0000-0003-0465-3773)
- Jörg Vogel (ORCID: https://orcid.org/0000-0003-2220-1404)
- Marianne Meyers (ORCID: https://orcid.org/0000-0003-0475-1373)
- José Alberto Molina‐Tijeras (ORCID: https://orcid.org/0000-0003-1554-9226)
- Jessica Karta (ORCID: https://orcid.org/0000-0002-4674-0720)
- Monica Gabola (ORCID: https://orcid.org/0000-0002-5617-251X)
- Elisabeth Letellier (ORCID: https://orcid.org/0000-0001-8242-9393)
- Falk Ponath (ORCID: https://orcid.org/0000-0002-2144-0545)
- Eliane Klein (ORCID: https://orcid.org/0000-0003-1433-9710)
- Paul Wilmes (ORCID: https://orcid.org/0000-0002-6478-2924)
- Paolo Nucíforo (ORCID: https://orcid.org/0000-0003-1380-0990)
- Fabien Rodriguez
- Eric Koncina (ORCID: https://orcid.org/0000-0003-4764-1510)
- L. Casanova (ORCID: https://orcid.org/0000-0002-6174-333X)
- Johannes Meiser (ORCID: https://orcid.org/0000-0002-9093-6210)
- Daniel Léonard (ORCID: https://orcid.org/0000-0002-9787-2133)
- Serge Haan
- Lidia Alonso
- Nikolaus Zügel
- Catarina Correia Tavares Bernardino
- Mònica Aguilera Pujabet
- Perla Saoud (ORCID: https://orcid.org/0000-0003-2611-3268)
- Eric Willemssen
- Philippe Koppes
Institutions
- Centre Hospitalier de Luxembourg (LU)
- University of Luxembourg (LU)
- University of Würzburg (DE)
- Luxembourg Institute of Health (LU)
- Luxembourg Institute of Science and Technology (LU)
- Helmholtz Centre for Infection Research (DE)
- Helmholtz Institute for RNA-based Infection Research (DE)
- Laboratoire National de Santé (LU)
- Arbed (Luxembourg) (LU)
- Vall d'Hebron Institute of Oncology (ES)
Publication Details
- Journal
- The EMBO Journal
- Published
- 2025-08-22
- DOI
- https://doi.org/10.1038/s44318-025-00542-w
- Citations
- 7
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- Université du Luxembourg
- Cancer Research UK
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fonds National de la Recherche Luxembourg
- Fonds De La Recherche Scientifique - FNRS
- Fondation Gustave et Simone Prévot