Association of Fusobacterium nucleatum with colorectal cancer molecular subtypes and its outcome: a systematic review

Abstract

Colorectal cancer (CRC) represents a relevant public health problem, with high incidence and mortality in Western countries. CRC can occur as sporadic (65%-75%), common familial (25%), or as a consequence of an inherited predisposition (up to 10%). While unravelling its genetic basis has been a long trip leading to relevant clinical implementation over more than 30 years, other contributing factors remain to be clarified. Among these, micro-organisms have emerged as critical players in the development and progression of the disease, as well as for CRC treatment response. Fusobacterium nucleatum (Fn) has been associated with CRC development in both pre-clinical models and clinical settings. Fusobacteria are core members of the human oral microbiome, while being less prevalent in the healthy gut, prompting questions about their localization in CRC and its precursor lesions. This review aims to critically discuss the evidence connecting Fn with CRC pathogenesis, its molecular subtypes and clinical outcomes.

Keywords: Fusobacterium nucleatum; colorectal cancer; microbiome; prognosis.

Created with BioRender.com – Last accessed online on 18 July 2024.

Figure 1.

The entry of Fn into mucosal epithelial cells relies on surface molecules such as lipopolysaccharides (LPS), adhesin A (FadA), and fusobacterium autotransporter protein 2 (Fap2). Fn targets cells expressing Gal-Gal-Nac via FadA, binds to E-cadherin, and is internalized by epithelial cells. Once inside, Fn releases its RNA into the host cell cytoplasm, which is detected by cytosolic retinoic acid-inducible gene 1 (RIG-1), activating the β-catenin and NF-kB signalling pathways through FadA-E-cadherin binding on TLR4. This FadA-E-cadherin interaction accelerates carcinogenesis in the presence of predisposing mutations. Meanwhile, Fap2-TIGIT binding promotes tumour survival by inhibiting anti-tumour immunity and contributing to chemotherapeutic resistance. Figure created by https://smart.servier.com. Last accessed online on 18 July 2024.