REFERENCES
1. Flavahan WA, Gaskell E, Bernstein BE. Epigenetic plasticity and the hallmarks of cancer. Science 2017;357:eaal2380.
2. Anfossi S, Calin GA. Gut microbiota: a new player in regulating immune- and chemo-therapy efficacy. Cancer Drug Resist 2020;3:356-70.
3. de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. The Lancet Oncology 2012;13:607-15.
4. Dzutsev A, Badger JH, Perez-Chanona E, et al. Microbes and cancer. Annu Rev Immunol 2017;35:199-228.
6. Lopez LR, Bleich RM, Arthur JC. Microbiota effects on carcinogenesis: initiation, promotion, and progression. Annu Rev Med 2021;72:243-61.
7. Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum 2012;100:1-441.
8. Hashemi Goradel N, Heidarzadeh S, Jahangiri S, et al. Fusobacterium nucleatum and colorectal cancer: a mechanistic overview. J Cell Physiol 2019;234:2337-44.
9. Mager DL, Haffajee AD, Devlin PM, Norris CM, Posner MR, Goodson JM. The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J Transl Med 2005;3:27.
10. Crowe SE. Helicobacter infection, chronic inflammation, and the development of malignancy. Curr Opin Gastroenterol 2005;21:32-8.
11. Montalban C, Santon A, Boixeda D, Bellas C. Regression of gastric high grade mucosa associated lymphoid tissue (MALT) lymphoma after Helicobacter pylori eradication. Gut 2001;49:584-7.
12. Dutta U, Garg PK, Kumar R, Tandon RK. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am J Gastroenterol 2000;95:784-7.
13. Mann EH, Maughan TS. Fusobacterium nucleatum, rectal cancer and radiotherapy. Ann Oncol 2020;31:1277-8.
14. Huang ST, Chen J, Lian LY, et al. Intratumoral levels and prognostic significance of Fusobacterium nucleatum in cervical carcinoma. Aging (Albany NY) 2020;12:23337-50.
15. Brennan CA, Garrett WS. Fusobacterium nucleatum-symbiont, opportunist and oncobacterium. Nat Rev Microbiol 2019;17:156-66.
16. Fan X, Alekseyenko AV, Wu J, et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut 2018;67:120-7.
17. Yamamura K, Baba Y, Nakagawa S, et al. Human microbiome fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res 2016;22:5574-81.
18. Mitsuhashi K, Nosho K, Sukawa Y, et al. Association of fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget 2015;6:7209-20.
19. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci 2017;18:197.
20. Loeb LA, Harris CC. Advances in chemical carcinogenesis: a historical review and prospective. Cancer Res 2008;68:6863-72.
21. Loozen G, Ozcelik O, Boon N, et al. Inter-bacterial correlations in subgingival biofilms: a large-scale survey. J Clin Periodontol 2014;41:1-10.
22. Field CA, Gidley MD, Preshaw PM, Jakubovics N. Investigation and quantification of key periodontal pathogens in patients with type 2 diabetes. J Periodontal Res 2012;47:470-8.
23. Griffen AL, Beall CJ, Campbell JH, et al. Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing. ISME J 2012;6:1176-85.
25. Parhi L, Alon-Maimon T, Sol A, et al. Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression. Nat Commun 2020;11:3259.
26. Cochrane K, Robinson AV, Holt RA, Allen-Vercoe E. A survey of Fusobacterium nucleatum genes modulated by host cell infection. Microb Genom 2020;6:e000300.
27. Han YW. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol 2015;23:141-7.
28. Kaplan A, Kaplan CW, He X, McHardy I, Shi W, Lux R. Characterization of aid1, a novel gene involved in Fusobacterium nucleatum interspecies interactions. Microb Ecol 2014;68:379-87.
29. Kaplan CW, Ma X, Paranjpe A, et al. Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes. Infect Immun 2010;78:4773-8.
30. Kaplan CW, Lux R, Haake SK, Shi W. The Fusobacterium nucleatum outer membrane protein RadD is an arginine-inhibitable adhesin required for inter-species adherence and the structured architecture of multispecies biofilm. Mol Microbiol 2009;71:35-47.
31. Xu M, Yamada M, Li M, Liu H, Chen SG, Han YW. FadA from fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells. J Biol Chem 2007;282:25000-9.
32. Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 2013;14:195-206.
33. Fardini Y, Wang X, Témoin S, et al. Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity. Mol Microbiol 2011;82:1468-80.
34. Gumbiner BM. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol 2005;6:622-34.
35. Sakai S, Aimi N, Endo J, et al. Transformation of indole alkaloids. IV. Reinvestigation of C/D ring closing reaction on indole alkaloid synthesis and the synthesis of heteroyohimbines, aricine and reserpine (author’s transl). Yakugaku Zasshi 1978;98:850-62.
36. Coppenhagen-Glazer S, Sol A, Abed J, et al. Fap2 of fusobacterium nucleatum is a galactose-inhibitable adhesin involved in coaggregation, cell adhesion, and preterm birth. Infect Immun 2015;83:1104-13.
37. Abed J, Emgård JE, Zamir G, et al. Fap2 mediates fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc. Cell Host Microbe 2016;20:215-25.
38. Gur C, Ibrahim Y, Isaacson B, et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 2015;42:344-55.
39. Okita Y, Koi M, Takeda K, et al. Fusobacterium nucleatum infection correlates with two types of microsatellite alterations in colorectal cancer and triggers DNA damage. Gut Pathog 2020;12:46.
40. Xia X, Wu WKK, Wong SH, et al. Bacteria pathogens drive host colonic epithelial cell promoter hypermethylation of tumor suppressor genes in colorectal cancer. Microbiome 2020;8:108.
41. Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 2006;38:787-93.
42. Koi M, Okita Y, Carethers JM. Fusobacterium nucleatum infection in colorectal cancer: linking inflammation, DNA mismatch repair and genetic and epigenetic alterations. J Anus Rectum Colon 2018;2:37-46.
43. Kelly D, Yang L, Pei Z. Gut microbiota, fusobacteria, and colorectal cancer. Diseases 2018;6:109.
44. Mima K, Cao Y, Chan AT, et al. Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location. Clin Transl Gastroenterol 2016;7:e200.
45. Mima K, Nishihara R, Qian ZR, et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut 2016;65:1973-80.
46. Ito M, Kanno S, Nosho K, et al. Association of fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway. Int J Cancer 2015;137:1258-68.
47. Tahara T, Yamamoto E, Suzuki H, et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res 2014;74:1311-8.
48. Lee DW, Han SW, Kang JK, et al. Association between fusobacterium nucleatum, pathway mutation, and patient prognosis in colorectal cancer. Ann Surg Oncol 2018;25:3389-95.
49. Guo P, Tian Z, Kong X, et al. FadA promotes DNA damage and progression of fusobacterium nucleatum-induced colorectal cancer through up-regulation of chk2. J Exp Clin Cancer Res 2020;39:202.
50. Geng F, Zhang Y, Lu Z, Zhang S, Pan Y. Fusobacterium nucleatum caused DNA damage and promoted cell proliferation by the Ku70/p53 pathway in oral cancer cells. DNA Cell Biol 2020;39:144-51.
51. Jorissen RN, Lipton L, Gibbs P, et al. DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers. Clin Cancer Res 2008;14:8061-9.
52. Sayed IM, Chakraborty A, Abd El-Hafeez AA, et al. The DNA glycosylase NEIL2 suppresses fusobacterium-infection-induced inflammation and DNA damage in colonic epithelial cells. Cells 2020;9:1980.
53. Chen Y, Peng Y, Yu J, et al. Invasive fusobacterium nucleatum activates beta-catenin signaling in colorectal cancer via a TLR4/P-PAK1 cascade. Oncotarget 2017;8:31802-14.
54. Dharmani P, Strauss J, Ambrose C, Allen-Vercoe E, Chadee K. Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha. Infect Immun 2011;79:2597-607.
55. Yang Y, Weng W, Peng J, et al. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21. Gastroenterology 2017;152:851-866.e24.
56. Su Y, Chen C, Guo L, Du J, Li X, Liu Y. Ecological balance of oral microbiota is required to maintain oral mesenchymal stem cell homeostasis. Stem Cells 2018;36:551-61.
57. Quah SY, Bergenholtz G, Tan KS. Fusobacterium nucleatum induces cytokine production through Toll-like-receptor-independent mechanism. Int Endod J 2014;47:550-9.
58. Fujiwara N, Kitamura N, Yoshida K, Yamamoto T, Ozaki K, Kudo Y. Involvement of fusobacterium species in oral cancer progression: a literature review including other types of cancer. Int J Mol Sci 2020;21:6207.
59. Sasabe E, Tomomura A, Kitamura N, Yamamoto T. Metal nanoparticles-induced activation of NLRP3 inflammasome in human oral keratinocytes is a possible mechanism of oral lichenoid lesions. Toxicol In Vitro 2020;62:104663.
60. Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 2013;14:207-15.
61. Stanietsky N, Simic H, Arapovic J, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A 2009;106:17858-63.
62. Mima K, Sukawa Y, Nishihara R, et al. Fusobacterium nucleatum and T cells in colorectal carcinoma. JAMA Oncol 2015;1:653-61.
63. Wang N, Feng Y, Wang Q, et al. Neutrophils infiltration in the tongue squamous cell carcinoma and its correlation with CEACAM1 expression on tumor cells. PLoS One 2014;9:e89991.
64. Gray-Owen SD, Blumberg RS. CEACAM1: contact-dependent control of immunity. Nat Rev Immunol 2006;6:433-46.
65. Gur C, Maalouf N, Shhadeh A, et al. Fusobacterium nucleatum supresses anti-tumor immunity by activating CEACAM1. Oncoimmunology 2019;8:e1581531.
66. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012;12:253-68.
67. Sun HL, Zhou X, Xue YF, et al. Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma. World J Gastroenterol 2012;18:3303-9.
68. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 2012;30:531-64.
69. Gulubova MV, Ananiev JR, Vlaykova TI, Yovchev Y, Tsoneva V, Manolova IM. Role of dendritic cells in progression and clinical outcome of colon cancer. Int J Colorectal Dis 2012;27:159-69.
70. Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 2010;22:231-7.
71. Lancy P Jr, Dirienzo JM, Appelbaum B, Rosan B, Holt SC. Corncob formation between fusobacterium nucleatum and streptococcus sanguis. Infect Immun 1983;40:303-9.
72. Bullman S, Pedamallu CS, Sicinska E, et al. Analysis of fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017;358:1443-8.
73. Warren RL, Freeman DJ, Pleasance S, et al. Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome 2013;1:16.
74. Binder Gallimidi A, Fischman S, Revach B, et al. Periodontal pathogens porphyromonas gingivalis and fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Oncotarget 2015;6:22613-23.
75. Saito A, Kokubu E, Inagaki S, et al. Porphyromonas gingivalis entry into gingival epithelial cells modulated by fusobacterium nucleatum is dependent on lipid rafts. Microb Pathog 2012;53:234-42.
76. Metzger Z, Lin YY, Dimeo F, Ambrose WW, Trope M, Arnold RR. Synergistic pathogenicity of porphyromonas gingivalis and fusobacterium nucleatum in the mouse subcutaneous chamber model. J Endod 2009;35:86-94.
77. Harrandah AM, Chukkapalli SS, Bhattacharyya I, Progulske-Fox A, Chan EKL. Fusobacteria modulate oral carcinogenesis and promote cancer progression. J Oral Microbiol 2020;13:1849493.
78. Yan X, Liu L, Li H, Qin H, Sun Z. Clinical significance of fusobacterium nucleatum, epithelial-mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients. Onco Targets Ther 2017;10:5031-46.
79. Yu MR, Kim HJ, Park HR. Fusobacterium nucleatum accelerates the progression of colitis-associated colorectal cancer by promoting EMT. Cancers (Basel) 2020;12:2728.
80. Allison SE, Chen Y, Petrovic N, et al. Activation of ALDH1A1 in MDA-MB-468 breast cancer cells that over-express CYP2J2 protects against paclitaxel-dependent cell death mediated by reactive oxygen species. Biochem Pharmacol 2017;143:79-89.
81. Karkhanis A, Hong Y, Chan ECY. Inhibition and inactivation of human CYP2J2: implications in cardiac pathophysiology and opportunities in cancer therapy. Biochem Pharmacol 2017;135:12-21.
82. Wang W, Yang J, Edin ML, et al. Targeted metabolomics identifies the cytochrome P450 monooxygenase eicosanoid pathway as a novel therapeutic target of colon tumorigenesis. Cancer Res 2019;79:1822-30.
83. Kong C, Yan X, Zhu Y, et al. Fusobacterium nucleatum promotes the development of colorectal cancer by activating a cytochrome P450/Epoxyoctadecenoic acid axis via TLR4/Keap1/NRF2 signaling. Cancer Res 2021;81:4485-98.
85. Bednarz-Knoll N, Alix-Panabières C, Pantel K. Plasticity of disseminating cancer cells in patients with epithelial malignancies. Cancer Metastasis Rev 2012;31:673-87.
86. Zhang S, Li C, Liu J, et al. Fusobacterium nucleatum promotes epithelial-mesenchymal transiton through regulation of the lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 signaling pathway. FEBS J 2020;287:4032-47.
87. Yang Y, Jobin C. Far reach of fusobacterium nucleatum in cancer metastasis. Gut 2020; doi: 10.1136/gutjnl-2020-323496.
88. Chen Y, Chen Y, Zhang J, et al. Fusobacterium nucleatum promotes metastasis in colorectal cancer by activating autophagy signaling via the upregulation of CARD3 expression. Theranostics 2020;10:323-39.
89. Chen S, Su T, Zhang Y, et al. Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating KRT7-AS/KRT7. Gut Microbes 2020;11:511-25.
90. Casasanta MA, Yoo CC, Udayasuryan B, et al. Fusobacterium nucleatum host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration. Sci Signal 2020;13:eaba9157.
91. Xu C, Fan L, Lin Y, et al. Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization. Gut Microbes 2021;13:1980347.
92. Guo S, Chen J, Chen F, Zeng Q, Liu WL, Zhang G. Exosomes derived from fusobacterium nucleatum-infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16. Gut 2020; doi: 10.1136/gutjnl-2020-321187.
93. Ellis TN, Kuehn MJ. Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiol Mol Biol Rev 2010;74:81-94.
94. Chatterjee D, Chaudhuri K. Vibrio cholerae O395 outer membrane vesicles modulate intestinal epithelial cells in a NOD1 protein-dependent manner and induce dendritic cell-mediated Th2/Th17 cell responses. J Biol Chem 2013;288:4299-309.
95. Mendes RT, Nguyen D, Stephens D, et al. Endothelial cell response to fusobacterium nucleatum. Infect Immun 2016;84:2141-8.
96. Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of fusobacterium with colorectal carcinoma. Genome Res 2012;22:292-8.
97. Yamamura K, Izumi D, Kandimalla R, et al. Intratumoral fusobacterium nucleatum levels predict therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma. Clin Cancer Res 2019;25:6170-9.
98. Serna G, Ruiz-Pace F, Hernando J, et al. Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer. Ann Oncol 2020;31:1366-75.
99. Yi Y, Shen L, Shi W, et al. Gut microbiome components predict response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a prospective, longitudinal study. Clin Cancer Res 2021;27:1329-40.
100. Zheng DW, Dong X, Pan P, et al. Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy. Nat Biomed Eng 2019;3:717-28.
101. Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 2017;170:548-563.e16.
102. Liu Y, Baba Y, Ishimoto T, et al. Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma. Br J Cancer 2021;124:963-74.
103. Duvvuri U, Shiwarski DJ, Xiao D, et al. TMEM16A induces MAPK and contributes directly to tumorigenesis and cancer progression. Cancer Res 2012;72:3270-81.
104. Karasawa H, Miura K, Fujibuchi W, et al. Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells. Cancer Sci 2009;100:903-13.
105. Park SM, Yoon JB, Lee TH. Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro. FEBS Lett 2004;566:151-6.
106. Zhang S, Yang Y, Weng W, et al. Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer. J Exp Clin Cancer Res 2019;38:14.
107. Lu P, Xu M, Xiong Z, Zhou F, Wang L. Fusobacterium nucleatum prevents apoptosis in colorectal cancer cells via the ANO1 pathway. Cancer Manag Res 2019;11:9057-66.
108. Onozawa H, Saito M, Saito K, et al. Annexin A1 is involved in resistance to 5-FU in colon cancer cells. Oncol Rep 2017;37:235-40.
109. Ding W, Tong Y, Zhang X, Pan M, Chen S. Study of arsenic sulfide in solid tumor cells reveals regulation of nuclear factors of activated T-cells by PML and p53. Sci Rep 2016;6:19793.
110. Da J, Wang X, Li L, Xu Y. Fusobacterium nucleatum promotes cisplatin-resistance and migration of oral squamous carcinoma cells by up-regulating Wnt5a-mediated NFATc3 expression. Tohoku J Exp Med 2021;253:249-59.
111. Liu PF, Huang IF, Shu CW, Huang CM. Halitosis vaccines targeting FomA, a biofilm-bridging protein of fusobacteria nucleatum. Curr Mol Med 2013;13:1358-67.
112. Strauss J, Kaplan GG, Beck PL, et al. Invasive potential of gut mucosa-derived fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis 2011;17:1971-8.