INTERNATIONAL CONGRESS OF
CancerGenetics
Wnt/β-catenin Signaling Pathway Mediated by the Gut Microbiome: The Influence of Fusobacterium nucleatum on Colorectal Cancer Progression
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Mahsa Nahavandi ,1 Aida Kamran,2 Vahideh Keyvani,3,*
1. Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
2. Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Ira
3. Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
- Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide, which is urgently needs of improved prevention and treatment strategies. The microbiome, consisting of diverse microorganism communities including viruses, bacteria, fungi, and eukaryotes colonizing human body surfaces, has recently been identified as a contributor to inter-individual variation through its unique, person-specific signatures. Fusobacterium nucleatum, an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in CRC progression and prognosis. The Wnt/β-catenin signaling pathway normally maintains cellular and tissue homeostasis by regulating cellular differentiation and survival in a controlled manner.
- Methods: This review was conducted by analyzing articles published in PubMed, Google Scholar, and Science Direct from 2022 to June 2025. The search keywords included ‘microbiome’, ‘fFusobacterium nucleatum’, ‘metabolic pathway’ and ‘colorectal cancer’”. By searching these three databases, more than 50 articles were reviewed, 30 were excluded based on the inclusion criteria, resulting in 20 articles retained for further review. Only English-language articles were chosen.
- Results: Finally, 15 articles were selected in the study. Evidence has revealed the gut microbiota and its metabolites interact closely with host epithelial cells and have a crucial role in CRC and are an important part of the tumor microenvironment. Gut microbiota dysbiosis can reshape the tumor microenvironment and make it more favorable for tumor growth. The mechanisms involved include increasing mutagenesis, regulation of oncogenic pathways, and modulation of the host immune system. F. nucleatum is a harmful bacterium that secretes extracellular vesicles carrying active substances from parental bacteria, which are endocytosed by colon cancer cells and plays an important regulatory role in the oncogenic microbial environment of the colon. Additionally, this bacterium has been shown to increase the expression levels of inflammatory genes, transcription factors, and oncogenes." In CRC tissues, deregulation of the Wnt/β-catenin pathway is observed, indicating that its aberrant activation directly promotes CRC malignancy, cell migration, angiogenesis, chemoresistance, and a shorter patient lifespan. This signaling pathway can transform into an oncogenic pathway associated with Colorectal colorectal cancer. Growing evidence suggests that human commensal microbes are strongly associated with carcinogenesis, particularly the prevalence and high enrichment of Fusobacterium nucleatum in CRC progression. Notably, F. nucleatum targets the Wnt/β-catenin pathway by employing its adhesin to bind to E-cadherin, thereby initiating infection. Results showed that intestinal microbial homeostasis was gradually dysregulated, and the abundance of Fusobacterium was higher in CRC patients.
- Conclusion: In the present study, we showed the role of F. nucleatum in the development of CRC and the association between the gut microbiome and the expression of oncogenic signaling pathways. Also, Analysis analysis and review for of the Wnt/β-catenin pathway can be a potential target for this treatment and the other related cancers. Nevertheless, the role of Fusobacterium nucleatum in CRC initiation and progression remains to be investigated.
- Keywords: Fusobacterium nucleatum, Microbiome, Metabolic Pathway, Wnt/β-catenin Signaling Pathway, Colorectal
