TABLE 2.
Etiological studies of F. nucleatum in CRC mouse models.
| CRC stage | F. nucleatum strain | CRC mouse models | F. nucleatum administration route | Findings/mechanisms | References |
| Tumor progression | ATCC 12230 (FadAc, mFadA, US1) | Nude mice HCT116 subcutaneously | Intratumor injection | Induces oncogenic and inflammatory responses via FadA | Rubinstein Mara et al. (2013) |
| APC Min+ mice | Oral gavage | Activates the Wnt/β-catenin oncogenic pathway via FadA | Rubinstein et al. (2019) | ||
| ATCC 25586 (US1) | Nude mice HCT116 subcutaneously | Intratumor injection | Promotes high glucose metabolism to provide energy for tumorigenesis | Hong et al. (2020) | |
| Nude mice HT29/HCT116/Lovo subcutaneously | Co-cultured | Causes DNA damage via FadA Induces miR-21 to activate the MAPK oncogenic pathway | Yang et al. (2017); Guo P. et al., 2020; Guo P. et al., 2020 | ||
| APCMin+ mice | Oral gavage | Causes DNA damage via FadA Induces miR-21 to activate the MAPK oncogenic pathway Activates the JAK/STAT and MAPK/ERK pathways | Yu et al. (2015); Yang et al. (2017); Guo et al., 2020 | ||
| WT mice AOM/DSS | Oral gavage | Induces miR-21 to activate the MAPK oncogenic pathway | Yang et al. (2017) | ||
| WT mice DMH | Oral gavage | Activates the JAK/STAT and MAPK/ERK pathways | Yu et al. (2015) | ||
| F01 | APC Min+ mice | Oral gavage | Promotes M2 polarization of macrophages Via a TLR4/p-PAK1/p-β-catenin S675 cascade | Chen et al. (2018); Wu et al. (2018) | |
| COCA36F3 | Human-derived xenografts | / | Metronidazole reduces F. nucleatum load and tumor growth | Bullman et al. (2017) | |
| EAVG_002 | APC Min+ mice | Oral gavage | Modulates the tumor-infiltrating immune cells | Kostic et al. (2013) | |
| IL-10–/– mice | Oral gavage | No findings | Kostic et al. (2013) | ||
| T-bet–/–× Rag2–/– mice | Oral gavage | No findings | Kostic et al. (2013) | ||
| CC53, CC7/3JVN3C1, CC7/5JVN1A4, CC2/3Fmu1, CC2/3FmuA, CC7/4Fmu3 | APC Min+; IL-10–/– mice (GF) | Oral gavage | No findings | Tomkovich et al. (2017) | |
| APC Min+ mice (GF) | Oral gavage | No findings | Tomkovich et al. (2017) | ||
| CC7/4Fmu3 | APC Min+ mice (GF) | Oral gavage | No findings | Tomkovich et al. (2017) | |
| Tumor metastasis | ATCC 25586 | Nude mice HCT116 tail vein injection | Co-cultured | Modulates KRT7-AS/KRT7 to promote metastasis | Chen S. et al., 2020 |
| Nude mice HCT116 subcutaneously | Exosomes* Intratumor injection | Stimulates cancer cells to generate miR-1246/92b-3p/27a-3p-rich exosomes to promote non-infected cancer cells migration | Guo S. et al., 2020 | ||
| Nude mice CT26 tail vein injection | Exosomes* Tail vein injection | Stimulates cancer cells to generate miR-1246/92b-3p/27a-3p-rich exosomes to promote non-infected cancer cells migration | Guo S. et al., 2020 | ||
| F01 | WT mice CT26 tail vein injection | Co-cultured | Activates cancer-related autophagy by upregulating CARD3 expression | Chen Y. et al. (2020) | |
| Chemoresistance | ATCC 25586 | Nude mice HCT116/SW480 Subcutaneously | Intratumor injection | Downregulates miR-18a* and miR-4802 then activates the autophagy pathway Upregulates BIRC3 gene via TLR4/NF-κB pathway then inhibits apoptosis | Yu et al. (2017); Zhang et al. (2019) |
| Translocation and colonization | ATCC 23726 (K50, D22, CTI-2, CTI-7) | WT mice Orthotopic rectal CT26 intravenous injection | Tail vein injection | Translocates to CRC tissue by blood-borne The colonization is Fap2 dependent | Abed et al. (2016) |
| APC Min+ mice | Tail vein injection | The colonization is Fap2 dependent | Abed et al. (2016) |
*Exosomes, isolated from the supernatant of F. nucleatum-infected HCT116 cells.
WT, wild-type; AOM, azoxymethane; DSS, dextran sodium sulfate; DMH, 1,2-dimethylhydrazine; GF, germ-free.