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<p>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 <i>Fusobacterium nucleatum</i> and cancer-associated fibroblasts (CAFs), and show that <i>F. nucleatum</i> is present in the stromal compartment in murine CRC models in vivo and can attach to and invade CAFs. <i>F. nucleatum</i>-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 <i>F. nucleatum</i>-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.</p>

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Fusobacterium nucleatum interacts with cancer-associated fibroblasts to promote colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月22日

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  • Jessica Karta,
  • Marianne Meyers,
  • Fabien Rodriguez,
  • Eric Koncina,
  • Cedric Gilson,
  • Eliane Klein,
  • Monica Gabola,
  • Mohaned Benzarti,
  • Pau Pérez Escriva,
  • Jose Alberto Molina Tijeras,
  • Catarina Correia Tavares Bernardino,
  • Falk Ponath,
  • Anais Carpentier,
  • Mònica Aguilera Pujabet,
  • Maryse Schmoetten,
  • Mina Tsenkova,
  • Perla Saoud,
  • Anthoula Gaigneaux,
  • Dominik Ternes,
  • Lidia Alonso,
  • Nikolaus Zügel,
  • Eric Willemssen,
  • Philippe Koppes,
  • Daniel Léonard,
  • Luis Perez Casanova,
  • Serge Haan,
  • Michel Mittelbronn,
  • Johannes Meiser,
  • Vitaly I Pozdeev,
  • Jörg Vogel,
  • Paolo G Nuciforo,
  • Paul Wilmes,
  • Elisabeth Letellier

摘要

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.