Fusobacterium nucleatum: a new player in regulation of cancer development and therapeutic response

Tengda Zhao , Xueping Wang , Liwu Fu , Ke Yang

Cancer Drug Resistance ›› 2022, Vol. 5 ›› Issue (2) : 436 -50.

PDF
Cancer Drug Resistance ›› 2022, Vol. 5 ›› Issue (2) :436 -50. DOI: 10.20517/cdr.2021.144
review-article

Fusobacterium nucleatum: a new player in regulation of cancer development and therapeutic response

Author information +
History +
PDF

Abstract

A dysbiosis in microbial diversity or functionality can promote disease development. Emerging preclinical and clinical evidence emphasizes the interplay between microbiota and both disease evolution and the treatment response of different cancers. One bacterium that has garnered much attention in a few cancer microbiota studies is Fusobacterium nucleaum (Fn). To provide updated knowledge of the functional role of Fn in cancer prevention and management, this review summarizes the relationship among Fn, cancer, and chemoimmunotherapy response, with the potential mechanisms of action also intensively discussed, which will benefit the development of strategies to prevent or treat cancer via Fn-based therapeutic interventions.

Keywords

Fusobacterium nucleatum / tumor microenvironment / immune evasion / metastasis / chemoresistance

Cite this article

Download citation ▾
Tengda Zhao, Xueping Wang, Liwu Fu, Ke Yang. Fusobacterium nucleatum: a new player in regulation of cancer development and therapeutic response. Cancer Drug Resistance, 2022, 5(2): 436-50 DOI:10.20517/cdr.2021.144

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Flavahan WA,Bernstein BE.Epigenetic plasticity and the hallmarks of cancer.Science2017;357:eaal2380 PMCID:PMC5940341

[2]

Anfossi S.Gut microbiota: a new player in regulating immune- and chemo-therapy efficacy.Cancer Drug Resist2020;3:356-70 PMCID:PMC7556722

[3]

de Martel C,Franceschi S.Global burden of cancers attributable to infections in 2008: a review and synthetic analysis.The Lancet Oncology2012;13:607-15

[4]

Dzutsev A,Perez-Chanona E.Microbes and cancer.Annu Rev Immunol2017;35:199-228

[5]

Schwabe RF.The microbiome and cancer.Nat Rev Cancer2013;13:800-12 PMCID:PMC3986062

[6]

Lopez LR,Arthur JC.Microbiota effects on carcinogenesis: initiation, promotion, and progression.Annu Rev Med2021;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 Hum2012;100:1-441

[8]

Hashemi Goradel N,Jahangiri S.Fusobacterium nucleatum and colorectal cancer: a mechanistic overview.J Cell Physiol2019;234:2337-44

[9]

Mager DL,Devlin PM,Posner MR.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 Med2005;3:27 PMCID:PMC1226180

[10]

Crowe SE.Helicobacter infection, chronic inflammation, and the development of malignancy.Curr Opin Gastroenterol2005;21:32-8

[11]

Montalban C,Boixeda D.Regression of gastric high grade mucosa associated lymphoid tissue (MALT) lymphoma after Helicobacter pylori eradication.Gut2001;49:584-7 PMCID:PMC1728454

[12]

Dutta U,Kumar R.Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder.Am J Gastroenterol2000;95:784-7

[13]

Mann EH.Fusobacterium nucleatum, rectal cancer and radiotherapy.Ann Oncol2020;31:1277-8

[14]

Huang ST,Lian LY.Intratumoral levels and prognostic significance of Fusobacterium nucleatum in cervical carcinoma.Aging (Albany NY)2020;12:23337-50 PMCID:PMC7746363

[15]

Brennan CA.Fusobacterium nucleatum-symbiont, opportunist and oncobacterium.Nat Rev Microbiol2019;17:156-66 PMCID:PMC6589823

[16]

Fan X,Wu J.Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study.Gut2018;67:120-7 PMCID:PMC5607064

[17]

Yamamura K,Nakagawa S.Human microbiome fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis.Clin Cancer Res2016;22:5574-81

[18]

Mitsuhashi K,Sukawa Y.Association of fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.Oncotarget2015;6:7209-20 PMCID:PMC4466679

[19]

Mármol I,Pradilla Dieste A,Rodriguez Yoldi MJ.Colorectal carcinoma: a general overview and future perspectives in colorectal cancer.Int J Mol Sci2017;18:197 PMCID:PMC5297828

[20]

Loeb LA.Advances in chemical carcinogenesis: a historical review and prospective.Cancer Res2008;68:6863-72 PMCID:PMC2583449

[21]

Loozen G,Boon N.Inter-bacterial correlations in subgingival biofilms: a large-scale survey.J Clin Periodontol2014;41:1-10

[22]

Field CA,Preshaw PM.Investigation and quantification of key periodontal pathogens in patients with type 2 diabetes.J Periodontal Res2012;47:470-8

[23]

Griffen AL,Campbell JH.Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing.ISME J2012;6:1176-85 PMCID:PMC3358035

[24]

Moore WE.The bacteria of periodontal diseases.Periodontol 20001994;5:66-77

[25]

Parhi L,Sol A.Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression.Nat Commun2020;11:3259 PMCID:PMC7320135

[26]

Cochrane K,Holt RA.A survey of Fusobacterium nucleatum genes modulated by host cell infection.Microb Genom2020;6:e000300 PMCID:PMC7067209

[27]

Han YW.Fusobacterium nucleatum: a commensal-turned pathogen.Curr Opin Microbiol2015;23:141-7 PMCID:PMC4323942

[28]

Kaplan A,He X,Shi W.Characterization of aid1, a novel gene involved in Fusobacterium nucleatum interspecies interactions.Microb Ecol2014;68:379-87 PMCID:PMC4104215

[29]

Kaplan CW,Paranjpe A.Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes.Infect Immun2010;78:4773-8 PMCID:PMC2976331

[30]

Kaplan CW,Haake SK.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 Microbiol2009;71:35-47 PMCID:PMC2741168

[31]

Xu M,Li M,Chen SG.FadA from fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells.J Biol Chem2007;282:25000-9

[32]

Rubinstein MR,Liu W,Cai G.Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin.Cell Host Microbe2013;14:195-206 PMCID:PMC3770529

[33]

Fardini Y,Témoin S.Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity.Mol Microbiol2011;82:1468-80 PMCID:PMC3237733

[34]

Gumbiner BM.Regulation of cadherin-mediated adhesion in morphogenesis.Nat Rev Mol Cell Biol2005;6:622-34

[35]

Sakai S,Endo J.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 Zasshi1978;98:850-62

[36]

Coppenhagen-Glazer S,Abed J.Fap2 of fusobacterium nucleatum is a galactose-inhibitable adhesin involved in coaggregation, cell adhesion, and preterm birth.Infect Immun2015;83:1104-13 PMCID:PMC4333458

[37]

Abed J,Zamir G.Fap2 mediates fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc.Cell Host Microbe2016;20:215-25 PMCID:PMC5465824

[38]

Gur C,Isaacson B.Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack.Immunity2015;42:344-55 PMCID:PMC4361732

[39]

Okita Y,Takeda K.Fusobacterium nucleatum infection correlates with two types of microsatellite alterations in colorectal cancer and triggers DNA damage.Gut Pathog2020;12:46 PMCID:PMC7526104

[40]

Xia X,Wong SH.Bacteria pathogens drive host colonic epithelial cell promoter hypermethylation of tumor suppressor genes in colorectal cancer.Microbiome2020;8:108 PMCID:PMC7367367

[41]

Weisenberger DJ,Campan M.CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer.Nat Genet2006;38:787-93

[42]

Koi M,Carethers JM.Fusobacterium nucleatum infection in colorectal cancer: linking inflammation, DNA mismatch repair and genetic and epigenetic alterations.J Anus Rectum Colon2018;2:37-46 PMCID:PMC6090547

[43]

Kelly D,Pei Z.Gut microbiota, fusobacteria, and colorectal cancer.Diseases2018;6:109 PMCID:PMC6313651

[44]

Mima K,Chan AT.Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location.Clin Transl Gastroenterol2016;7:e200 PMCID:PMC5543402

[45]

Mima K,Qian ZR.Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis.Gut2016;65:1973-80 PMCID:PMC4769120

[46]

Ito M,Nosho K.Association of fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway.Int J Cancer2015;137:1258-68

[47]

Tahara T,Suzuki H.Fusobacterium in colonic flora and molecular features of colorectal carcinoma.Cancer Res2014;74:1311-8 PMCID:PMC4396185

[48]

Lee DW,Kang JK.Association between fusobacterium nucleatum, pathway mutation, and patient prognosis in colorectal cancer.Ann Surg Oncol2018;25:3389-95

[49]

Guo P,Kong X.FadA promotes DNA damage and progression of fusobacterium nucleatum-induced colorectal cancer through up-regulation of chk2.J Exp Clin Cancer Res2020;39:202 PMCID:PMC7523382

[50]

Geng F,Lu Z,Pan Y.Fusobacterium nucleatum caused DNA damage and promoted cell proliferation by the Ku70/p53 pathway in oral cancer cells.DNA Cell Biol2020;39:144-51 PMCID:PMC6978777

[51]

Jorissen RN,Gibbs P.DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers.Clin Cancer Res2008;14:8061-9 PMCID:PMC2605660

[52]

Sayed IM,Abd El-Hafeez AA.The DNA glycosylase NEIL2 suppresses fusobacterium-infection-induced inflammation and DNA damage in colonic epithelial cells.Cells2020;9:1980 PMCID:PMC7565382

[53]

Chen Y,Yu J.Invasive fusobacterium nucleatum activates beta-catenin signaling in colorectal cancer via a TLR4/P-PAK1 cascade.Oncotarget2017;8:31802-14 PMCID:PMC5458249

[54]

Dharmani P,Ambrose C,Chadee K.Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha.Infect Immun2011;79:2597-607 PMCID:PMC3191979

[55]

Yang Y,Peng J.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.Gastroenterology2017;152:851-866.e24 PMCID:PMC5555435

[56]

Su Y,Guo L,Li X.Ecological balance of oral microbiota is required to maintain oral mesenchymal stem cell homeostasis.Stem Cells2018;36:551-61 PMCID:PMC5876121

[57]

Quah SY,Tan KS.Fusobacterium nucleatum induces cytokine production through Toll-like-receptor-independent mechanism.Int Endod J2014;47:550-9

[58]

Fujiwara N,Yoshida K,Ozaki K.Involvement of fusobacterium species in oral cancer progression: a literature review including other types of cancer.Int J Mol Sci2020;21:6207 PMCID:PMC7504605

[59]

Sasabe E,Kitamura N.Metal nanoparticles-induced activation of NLRP3 inflammasome in human oral keratinocytes is a possible mechanism of oral lichenoid lesions.Toxicol In Vitro2020;62:104663

[60]

Kostic AD,Robertson L.Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment.Cell Host Microbe2013;14:207-15 PMCID:PMC3772512

[61]

Stanietsky N,Arapovic J.The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity.Proc Natl Acad Sci U S A2009;106:17858-63 PMCID:PMC2764881

[62]

Mima K,Nishihara R.Fusobacterium nucleatum and T cells in colorectal carcinoma.JAMA Oncol2015;1:653-61 PMCID:PMC4537376

[63]

Wang N,Wang Q.Neutrophils infiltration in the tongue squamous cell carcinoma and its correlation with CEACAM1 expression on tumor cells.PLoS One2014;9:e89991 PMCID:PMC3937421

[64]

Gray-Owen SD.CEACAM1: contact-dependent control of immunity.Nat Rev Immunol2006;6:433-46

[65]

Gur C,Shhadeh A.Fusobacterium nucleatum supresses anti-tumor immunity by activating CEACAM1.Oncoimmunology2019;8:e1581531 PMCID:PMC6492956

[66]

Gabrilovich DI,Bronte V.Coordinated regulation of myeloid cells by tumours.Nat Rev Immunol2012;12:253-68 PMCID:PMC3587148

[67]

Sun HL,Xue YF.Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma.World J Gastroenterol2012;18:3303-9 PMCID:PMC3391769

[68]

Josefowicz SZ,Rudensky AY.Regulatory T cells: mechanisms of differentiation and function.Annu Rev Immunol2012;30:531-64 PMCID:PMC6066374

[69]

Gulubova MV,Vlaykova TI,Tsoneva V.Role of dendritic cells in progression and clinical outcome of colon cancer.Int J Colorectal Dis2012;27:159-69

[70]

Mantovani A.Macrophages, innate immunity and cancer: balance, tolerance, and diversity.Curr Opin Immunol2010;22:231-7

[71]

Lancy P Jr,Appelbaum B,Holt SC.Corncob formation between fusobacterium nucleatum and streptococcus sanguis.Infect Immun1983;40:303-9 PMCID:PMC264849

[72]

Bullman S,Sicinska E.Analysis of fusobacterium persistence and antibiotic response in colorectal cancer.Science2017;358:1443-8 PMCID:PMC5823247

[73]

Warren RL,Pleasance S.Co-occurrence of anaerobic bacteria in colorectal carcinomas.Microbiome2013;1:16 PMCID:PMC3971631

[74]

Binder Gallimidi A,Revach B.Periodontal pathogens porphyromonas gingivalis and fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model.Oncotarget2015;6:22613-23 PMCID:PMC4673186

[75]

Saito A,Inagaki S.Porphyromonas gingivalis entry into gingival epithelial cells modulated by fusobacterium nucleatum is dependent on lipid rafts.Microb Pathog2012;53:234-42 PMCID:PMC3653298

[76]

Metzger Z,Dimeo F,Trope M.Synergistic pathogenicity of porphyromonas gingivalis and fusobacterium nucleatum in the mouse subcutaneous chamber model.J Endod2009;35:86-94

[77]

Harrandah AM,Bhattacharyya I,Chan EKL.Fusobacteria modulate oral carcinogenesis and promote cancer progression.J Oral Microbiol2020;13:1849493 PMCID:PMC7717872

[78]

Yan X,Li 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 Ther2017;10:5031-46 PMCID:PMC5652912

[79]

Yu MR,Park HR.Fusobacterium nucleatum accelerates the progression of colitis-associated colorectal cancer by promoting EMT.Cancers (Basel)2020;12:2728 PMCID:PMC7598280

[80]

Allison SE,Petrovic N.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 Pharmacol2017;143:79-89

[81]

Karkhanis A,Chan ECY.Inhibition and inactivation of human CYP2J2: implications in cardiac pathophysiology and opportunities in cancer therapy.Biochem Pharmacol2017;135:12-21

[82]

Wang W,Edin ML.Targeted metabolomics identifies the cytochrome P450 monooxygenase eicosanoid pathway as a novel therapeutic target of colon tumorigenesis.Cancer Res2019;79:1822-30 PMCID:PMC6467714

[83]

Kong C,Zhu Y.Fusobacterium nucleatum promotes the development of colorectal cancer by activating a cytochrome P450/Epoxyoctadecenoic acid axis via TLR4/Keap1/NRF2 signaling.Cancer Res2021;81:4485-98

[84]

Saitoh M.Involvement of partial EMT in cancer progression.J Biochem2018;164:257-64

[85]

Bednarz-Knoll N,Pantel K.Plasticity of disseminating cancer cells in patients with epithelial malignancies.Cancer Metastasis Rev2012;31:673-87

[86]

Zhang S,Liu J.Fusobacterium nucleatum promotes epithelial-mesenchymal transiton through regulation of the lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 signaling pathway.FEBS J2020;287:4032-47 PMCID:PMC7540502

[87]

Yang Y.Far reach of fusobacterium nucleatum in cancer metastasis.Gut2020;

[88]

Chen Y,Zhang J.Fusobacterium nucleatum promotes metastasis in colorectal cancer by activating autophagy signaling via the upregulation of CARD3 expression.Theranostics2020;10:323-39 PMCID:PMC6929621

[89]

Chen S,Zhang Y.Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating KRT7-AS/KRT7.Gut Microbes2020;11:511-25 PMCID:PMC7524269

[90]

Casasanta MA,Udayasuryan B.Fusobacterium nucleatum host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration.Sci Signal2020;13:eaba9157 PMCID:PMC7454160

[91]

Xu C,Lin Y.Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization.Gut Microbes2021;13:1980347 PMCID:PMC8510564

[92]

Guo S,Chen F,Liu WL.Exosomes derived from fusobacterium nucleatum-infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16.Gut2020;

[93]

Ellis TN.Virulence and immunomodulatory roles of bacterial outer membrane vesicles.Microbiol Mol Biol Rev2010;74:81-94 PMCID:PMC2832350

[94]

Chatterjee D.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 Chem2013;288:4299-309 PMCID:PMC3567681

[95]

Mendes RT,Stephens D.Endothelial cell response to fusobacterium nucleatum.Infect Immun2016;84:2141-8 PMCID:PMC4936358

[96]

Kostic AD,Pedamallu CS.Genomic analysis identifies association of fusobacterium with colorectal carcinoma.Genome Res2012;22:292-8 PMCID:PMC3266036

[97]

Yamamura K,Kandimalla R.Intratumoral fusobacterium nucleatum levels predict therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma.Clin Cancer Res2019;25:6170-9 PMCID:PMC6801075

[98]

Serna G,Hernando J.Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer.Ann Oncol2020;31:1366-75 PMCID:PMC7542577

[99]

Yi Y,Shi W.Gut microbiome components predict response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a prospective, longitudinal study.Clin Cancer Res2021;27:1329-40

[100]

Zheng DW,Pan P.Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy.Nat Biomed Eng2019;3:717-28

[101]

Yu T,Yu Y.Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy.Cell2017;170:548-563.e16 PMCID:PMC5767127

[102]

Liu Y,Ishimoto T.Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma.Br J Cancer2021;124:963-74 PMCID:PMC7921654

[103]

Duvvuri U,Xiao D.TMEM16A induces MAPK and contributes directly to tumorigenesis and cancer progression.Cancer Res2012;72:3270-81 PMCID:PMC3694774

[104]

Karasawa H,Fujibuchi W.Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells.Cancer Sci2009;100:903-13

[105]

Park SM,Lee TH.Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro.FEBS Lett2004;566:151-6

[106]

Zhang S,Weng W.Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer.J Exp Clin Cancer Res2019;38:14 PMCID:PMC6327560

[107]

Lu P,Xiong Z,Wang L.Fusobacterium nucleatum prevents apoptosis in colorectal cancer cells via the ANO1 pathway.Cancer Manag Res2019;11:9057-66 PMCID:PMC6829176

[108]

Onozawa H,Saito K.Annexin A1 is involved in resistance to 5-FU in colon cancer cells.Oncol Rep2017;37:235-40

[109]

Ding W,Zhang X,Chen S.Study of arsenic sulfide in solid tumor cells reveals regulation of nuclear factors of activated T-cells by PML and p53.Sci Rep2016;6:19793 PMCID:PMC4726130

[110]

Da J,Li L.Fusobacterium nucleatum promotes cisplatin-resistance and migration of oral squamous carcinoma cells by up-regulating Wnt5a-mediated NFATc3 expression.Tohoku J Exp Med2021;253:249-59

[111]

Liu PF,Shu CW.Halitosis vaccines targeting FomA, a biofilm-bridging protein of fusobacteria nucleatum.Curr Mol Med2013;13:1358-67

[112]

Strauss J,Beck PL.Invasive potential of gut mucosa-derived fusobacterium nucleatum positively correlates with IBD status of the host.Inflamm Bowel Dis2011;17:1971-8

[113]

Tjalsma H,Marchesi JR.A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects.Nat Rev Microbiol2012;10:575-82

AI Summary AI Mindmap
PDF

103

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/