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. 2023 Apr 3;25:e15. doi: 10.1017/erm.2023.9

Figure 2.

Figure 2.

Known oncogenic pathways modulated by Fusobacterium nucleatum. F. nucleatum (shown in blue) binds to tumour cells via interaction of its Fap2 protein with D-galactose-β(1–3)-N-acetyl-D-galactosamine (Gal-GalNAc) or by FadA interacting with E-cadherin, which is enhanced by Annexin A1 (ANXA1), enabling attachment and invasion of tumour cells. F. nucleatum also secretes outer membrane vesicles (OMVs) and lipopolysaccharide (LPS) which interact with the Toll-like receptors (TLRs) to initiate downstream signalling pathways that mediate the release of inflammatory cytokines and transcription of miR-21 which is known to regulate the activity of the oncoprotein RASA1. The E-cadherin and TLR4 signalling induced by F. nucleatum binding stimulates β-catenin accumulation in the cytoplasm and its subsequent translocation to the nucleus where it upregulates transcription of oncogenes including c-MYC and Cyclin D1. Furthermore, F. nucleatum is able to aid metastasis through OMV-mediated degradation of E. cadherin, NF-κB mediated increased expression of keratin 7 (KRT7), and via induction of the inflammatory cytokines IL-8 and CXCL1. Figure created with BioRender.