1932

Abstract

Carcinogenesis is a multistep process by which normal cells acquire genetic and epigenetic changes that result in cancer. In combination with host genetic susceptibility and environmental exposures, a prominent procarcinogenic role for the microbiota has recently emerged. In colorectal cancer (CRC), three nefarious microbes have been consistently linked to cancer development: () Colibactin-producing initiates carcinogenic DNA damage, () enterotoxigenic promotes tumorigenesis via toxin-induced cell proliferation and tumor-promoting inflammation, and () enhances CRC progression through two adhesins, Fap2 and FadA, that promote proliferation and antitumor immune evasion and may contribute to metastases. Herein, we use these three prominent microbes to discuss the experimental evidence linking microbial activities to carcinogenesis and the specific mechanisms driving this stepwise process. Precisely defining mechanisms by which the microbiota impacts carcinogenesis at each stage is essential for developing microbiota-targeted strategies for the diagnosis, prognosis, and treatment of cancer.

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2021-01-27
2024-04-19
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Literature Cited

  1. 1. 
    Eckburg PB, Bik EM, Bernstein CN et al. 2005. Diversity of the human intestinal microbial flora. Science 308:57281635–38
    [Google Scholar]
  2. 2. 
    Backhed F, Ley RE, Sonnenburg JL et al. 2005. Host-bacterial mutualism in the human intestine. Science 307:57171915–20
    [Google Scholar]
  3. 3. 
    The Human Microbiome Project Consortium 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:7402207–14
    [Google Scholar]
  4. 4. 
    Lloyd-Price J, Mahurkar A, Rahnavard G et al. 2017. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 550:767461–66
    [Google Scholar]
  5. 5. 
    Costello EK, Lauber CL, Hamady M et al. 2009. Bacterial community variation in human body habitats across space and time. Science 326:59601694–97
    [Google Scholar]
  6. 6. 
    Levy R, Magis AT, Earls JC et al. 2020. Longitudinal analysis reveals transition barriers between dominant ecological states in the gut microbiome. PNAS 117:2413839–45
    [Google Scholar]
  7. 7. 
    Hamady M, Knight R. 2009. Microbial community profiling for human microbiome projects: tools, techniques, and challenges. Genome Res 19:71141–52
    [Google Scholar]
  8. 8. 
    Lozupone C, Knight R. 2005. UniFrac: a new phylogenetic method for comparing microbial communities. Appl. Environ. Microbiol. 71:128228–35
    [Google Scholar]
  9. 9. 
    Caporaso JG, Kuczynski J, Stombaugh J et al. 2010. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7:5335–36
    [Google Scholar]
  10. 10. 
    Lozupone CA, Stombaugh JI, Gordon JI et al. 2012. Diversity, stability and resilience of the human gut microbiota. Nature 489:7415220–30
    [Google Scholar]
  11. 11. 
    Zhao S, Lieberman TD, Poyet M et al. 2019. Adaptive evolution within gut microbiomes of healthy people. Cell Host Microbe 25:5656–58
    [Google Scholar]
  12. 12. 
    Vasapolli R, Schütte K, Schulz C et al. 2019. Analysis of transcriptionally active bacteria throughout the gastrointestinal tract of healthy individuals. Gastroenterology 157:41081–83
    [Google Scholar]
  13. 13. 
    Gilbert JA, Blaser MJ, Caporaso JG et al. 2018. Current understanding of the human microbiome. Nat. Med. 24:4392–400
    [Google Scholar]
  14. 14. 
    Dzutsev A, Badger JH, Perez-Chanona E et al. 2017. Microbes and cancer. Annu. Rev. Immunol. 35:199–228
    [Google Scholar]
  15. 15. 
    Fulbright LE, Ellermann M, Arthur JC 2017. The microbiome and the hallmarks of cancer. PLOS Pathog 13:9e1006480
    [Google Scholar]
  16. 16. 
    Wong SH, Yu J. 2019. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat. Rev. Gastroenterol. Hepatol. 16:11690–704
    [Google Scholar]
  17. 17. 
    Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell 144:5646–74
    [Google Scholar]
  18. 18. 
    Marshall BJ. 1995. The 1995 Albert Lasker Medical Research Award. Helicobacter pylori. The etiologic agent for peptic ulcer. JAMA 274:131064–66
    [Google Scholar]
  19. 19. 
    Marshall BJ, Warren JR. 1984. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1:83901311–15
    [Google Scholar]
  20. 20. 
    Amieva M, Peek RM Jr 2016. Pathobiology of Helicobacter pylori–induced gastric cancer. Gastroenterology 150:164–78
    [Google Scholar]
  21. 21. 
    Bhatt AP, Redinbo MR, Bultman SJ 2017. The role of the microbiome in cancer development and therapy. CA Cancer J. Clin. 67:4326–44
    [Google Scholar]
  22. 22. 
    O'Keefe SJD. 2016. Diet, microorganisms and their metabolites, and colon cancer. Nat. Rev. Gastroenterol. Hepatol. 13:12691–706
    [Google Scholar]
  23. 23. 
    Tsilimigras MCB, Fodor A, Jobin C 2017. Carcinogenesis and therapeutics: the microbiota perspective. Nat. Microbiol. 2:17008
    [Google Scholar]
  24. 24. 
    Tibbs TN, Lopez LR, Arthur JC 2019. The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging. Microb. Cell 6:8324–34
    [Google Scholar]
  25. 25. 
    Wong SH, Zhao L, Zhang X et al. 2017. Gavage of fecal samples from patients with colorectal cancer promotes intestinal carcinogenesis in germ-free and conventional mice. Gastroenterology 153:61621–33.e6
    [Google Scholar]
  26. 26. 
    Zackular JP, Baxter NT, Iverson KD et al. 2013. The gut microbiome modulates colon tumorigenesis. mBio 4:6e00692–13
    [Google Scholar]
  27. 27. 
    Tomkovich S, Dejea CM, Winglee K et al. 2019. Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic. J. Clin. Investig. 129:41699–712
    [Google Scholar]
  28. 28. 
    Schwabe RF, Jobin C. 2013. The microbiome and cancer. Nat. Rev. Cancer 13:11800–12
    [Google Scholar]
  29. 29. 
    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans 2012. Biological Agents: A Review of Human Carcinogens. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 100B Paris: Int. Agency Res. Cancer
    [Google Scholar]
  30. 30. 
    Loeb LA, Harris CC. 2008. Advances in chemical carcinogenesis: a historical review and prospective. Cancer Res 68:176863–72
    [Google Scholar]
  31. 31. 
    Donia MS, Fischbach MA. 2015. Small molecules from the human microbiota. Science 349:62461254766
    [Google Scholar]
  32. 32. 
    Nougayrede JP, Homburg S, Taieb F et al. 2006. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313:5788848–51
    [Google Scholar]
  33. 33. 
    Arthur JC, Perez-Chanona E, Mühlbauer M et al. 2012. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:6103120–23
    [Google Scholar]
  34. 34. 
    Buc E, Dubois D, Sauvanet P et al. 2013. High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer. PLOS ONE 8:2e56964
    [Google Scholar]
  35. 35. 
    Arthur JC, Gharaibeh RZ, Mühlbauer M et al. 2014. Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer. Nat. Commun. 5:4724
    [Google Scholar]
  36. 36. 
    Tomkovich S, Yang Y, Winglee K et al. 2017. Locoregional effects of microbiota in a preclinical model of colon carcinogenesis. Cancer Res 77:102620–32
    [Google Scholar]
  37. 37. 
    Cougnoux A, Dalmasso G, Martinez R et al. 2014. Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype. Gut 63:121932–42
    [Google Scholar]
  38. 38. 
    Pleguezuelos-Manzano C, Puschhof J, Huber AR et al. 2020. Mutational signature in colorectal cancer caused by genotoxic pks+E. coli. Nature 580:7802269–73
    [Google Scholar]
  39. 39. 
    Dziubańska-Kusibab PJ, Berger H, Battistini F et al. 2020. Colibactin DNA-damage signature indicates mutational impact in colorectal cancer. Nat. Med. 26:1063–69
    [Google Scholar]
  40. 40. 
    Homburg S, Oswald E, Hacker J et al. 2007. Expression analysis of the colibactin gene cluster coding for a novel polyketide in Escherichia coli. FEMS Microbiol. Lett 275:2255–62
    [Google Scholar]
  41. 41. 
    Faïs T, Delmas J, Barnich N et al. 2018. Colibactin: more than a new bacterial toxin. Toxins 10:4151
    [Google Scholar]
  42. 42. 
    Cuevas-Ramos G, Petit CR, Marcq I et al. 2010. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. PNAS 107:2511537–42
    [Google Scholar]
  43. 43. 
    Balskus EP. 2015. Colibactin: understanding an elusive gut bacterial genotoxin. Nat. Product Rep. 32:111534–40
    [Google Scholar]
  44. 44. 
    Bleich RM, Arthur JC. 2019. Revealing a microbial carcinogen. Science 363:6428689–90
    [Google Scholar]
  45. 45. 
    Wernke KM, Xue M, Tirla A et al. 2020. Structure and bioactivity of colibactin. Bioorg. Med. Chem. Lett. 30:15127280
    [Google Scholar]
  46. 46. 
    Cougnoux A, Gibold L, Robin F et al. 2012. Analysis of structure-function relationships in the colibactin-maturating enzyme ClbP. J. Mol. Biol. 424:3–4203–14
    [Google Scholar]
  47. 47. 
    Brotherton CA, Balskus EP. 2013. A prodrug resistance mechanism is involved in colibactin biosynthesis and cytotoxicity. J. Am. Chem. Soc. 135:93359–62
    [Google Scholar]
  48. 48. 
    Wilson MR, Jiang Y, Villalta PW et al. 2019. The human gut bacterial genotoxin colibactin alkylates DNA. Science 363:6428eaar7785
    [Google Scholar]
  49. 49. 
    Xue M, Kim CS, Healy AR et al. 2019. Structure elucidation of colibactin and its DNA cross-links. Science 365:6457eaax2685
    [Google Scholar]
  50. 50. 
    Vizcaino MI, Crawford JM. 2015. The colibactin warhead crosslinks DNA. Nat. Chem. 7:5411–17
    [Google Scholar]
  51. 51. 
    Kinzler KW, Vogelstein B. 1996. Lessons from hereditary colorectal cancer. Cell 87:2159–70
    [Google Scholar]
  52. 52. 
    Rowan AJ, Lamlum H, Ilyas M et al. 2000. APC mutations in sporadic colorectal tumors: a mutational “hotspot” and interdependence of the “two hits.”. PNAS 97:73352–57
    [Google Scholar]
  53. 53. 
    Lee-Six H, Olafsson S, Ellis P et al. 2019. The landscape of somatic mutation in normal colorectal epithelial cells. Nature 574:7779532–37
    [Google Scholar]
  54. 54. 
    Grivennikov SI, Wang K, Mucida D et al. 2012. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491:7423254–58
    [Google Scholar]
  55. 55. 
    Greten FR, Grivennikov SI. 2019. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity 51:127–41
    [Google Scholar]
  56. 56. 
    Valguarnera E, Wardenburg JB. 2020. Good gone bad: one toxin away from disease for Bacteroides fragilis. J. Mol. Biol. 432:4765–85
    [Google Scholar]
  57. 57. 
    Mazmanian SK, Round JL, Kasper DL 2008. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:7195620–25
    [Google Scholar]
  58. 58. 
    Round JL, Mazmanian SK. 2010. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. PNAS 107:2712204–9
    [Google Scholar]
  59. 59. 
    Sears CL, Geis AL, Housseau F 2014. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J. Clin. Investig. 124:104166–72
    [Google Scholar]
  60. 60. 
    Wu S, Rhee KJ, Albesiano E et al. 2009. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat. Med. 15:91016–22
    [Google Scholar]
  61. 61. 
    Wu S, Lim KC, Huang J et al. 1998. Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. PNAS 95:2514979–84
    [Google Scholar]
  62. 62. 
    Clevers H. 2006. Wnt/β-catenin signaling in development and disease. Cell 127:3469–80
    [Google Scholar]
  63. 63. 
    Hurtado CG, Wan F, Housseau F et al. 2018. Roles for interleukin 17 and adaptive immunity in pathogenesis of colorectal cancer. Gastroenterology 155:61706–15
    [Google Scholar]
  64. 64. 
    Wang K, Kim MK, Di Caro G et al. 2014. Interleukin-17 receptor A signaling in transformed enterocytes promotes early colorectal tumorigenesis. Immunity 41:61052–63
    [Google Scholar]
  65. 65. 
    Atarashi K, Tanoue T, Ando M et al. 2015. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:2367–80
    [Google Scholar]
  66. 66. 
    Han YW. 2015. Fusobacterium nucleatum: a commensal-turned pathogen. Curr. Opin. Microbiol. 23:141–47
    [Google Scholar]
  67. 67. 
    Strauss J, Kaplan GG, Beck PL et al. 2011. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm. Bowel Dis. 17:91971–78
    [Google Scholar]
  68. 68. 
    Allen-Vercoe E, Jobin C. 2014. Fusobacterium and Enterobacteriaceae: important players for CRC. Immunol. Lett. 162:254–61
    [Google Scholar]
  69. 69. 
    Cochrane K, Robinson AV, Holt RA et al. 2020. A survey of Fusobacterium nucleatum genes modulated by host cell infection. Microbial. Genom. 6:2e000300
    [Google Scholar]
  70. 70. 
    Parhi L, Alon-Maimon T, Sol A et al. 2020. Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression. Nat. Commun. 11:13259
    [Google Scholar]
  71. 71. 
    Kostic AD, Chun E, Robertson L et al. 2013. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14:2207–15
    [Google Scholar]
  72. 72. 
    Castellarin M, Warren RL, Freeman JD et al. 2011. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22:2299–306
    [Google Scholar]
  73. 73. 
    McCoy AN, Araujo-Perez F, Azcárate-Peril A et al. 2013. Fusobacterium is associated with colorectal adenomas. PLOS ONE 8:1e53653
    [Google Scholar]
  74. 74. 
    Mima K, Nishihara R, Qian ZR et al. 2016. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut 65:121973–80
    [Google Scholar]
  75. 75. 
    Kostic AD, Gevers D, Pedamallu CS et al. 2011. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:2292–98
    [Google Scholar]
  76. 76. 
    Bullman S, Pedamallu CS, Sicinska E et al. 2017. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 358:63691443–48
    [Google Scholar]
  77. 77. 
    Gur C, Ibrahim Y, Isaacson B et al. 2015. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42:2344–55
    [Google Scholar]
  78. 78. 
    Rubinstein MR, Wang X, Liu W et al. 2013. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 14:2195–206
    [Google Scholar]
  79. 79. 
    Casasanta MA, Yoo CC, Udayasuryan B et al. 2020. Fusobacterium nucleatum host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration. Sci. Signal. 13:641eaba9157
    [Google Scholar]
  80. 80. 
    Coppenhagen-Glazer S, Sol A, Abed J et al. 2015. Fap2 of Fusobacterium nucleatum is a galactose-inhibitable adhesin involved in coaggregation, cell adhesion, and preterm birth. Infect. Immunity 83:31104–13
    [Google Scholar]
  81. 81. 
    Abed J, Emgård JEM, Zamir G et al. 2016. Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc. Cell Host Microbe 20:2215–25
    [Google Scholar]
  82. 82. 
    Xu M, Yamada M, Li M et al. 2007. FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells. J. Biol. Chem. 282:3425000–9
    [Google Scholar]
  83. 83. 
    Manson McGuire A, Cochrane K, Griggs AD et al. 2014. Evolution of invasion in a diverse set of Fusobacterium species. mBio 5:6e01864
    [Google Scholar]
  84. 84. 
    Scott AJ, Alexander JL, Merrifield CA et al. 2019. International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis. Gut 68:91624–32
    [Google Scholar]
  85. 85. 
    Donohoe DR, Garge N, Zhang X et al. 2011. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab 13:5517–26
    [Google Scholar]
  86. 86. 
    Donohoe DR, Holley D, Collins LB et al. 2014. A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. Cancer Discov 4:121387–97
    [Google Scholar]
  87. 87. 
    Hale VL, Jeraldo P, Chen J et al. 2018. Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers. Genome Med 10:78
    [Google Scholar]
  88. 88. 
    Dejea CM, Fathi P, Craig JM et al. 2018. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359:6375592–97
    [Google Scholar]
  89. 89. 
    Dejea CM, Wick EC, Hechenbleikner EM et al. 2014. Microbiota organization is a distinct feature of proximal colorectal cancers. PNAS 111:5118321–26
    [Google Scholar]
  90. 90. 
    Xia J, Chiu L-Y, Nehring RB et al. 2019. Bacteria-to-human protein networks reveal origins of endogenous DNA damage. Cell 176:1–2127–143.e24
    [Google Scholar]
  91. 91. 
    Wang X, Huycke MM. 2007. Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology 132:2551–61
    [Google Scholar]
  92. 92. 
    Wang X, Allen TD, May RJ et al. 2008. Enterococcus faecalis induces aneuploidy and tetraploidy in colonic epithelial cells through a bystander effect. Cancer Res 68:239909–17
    [Google Scholar]
  93. 93. 
    Jia W, Xie G, Jia W 2017. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat. Rev. Gastroenterol. Hepatol. 15:2111–28
    [Google Scholar]
  94. 94. 
    Yang Y, Gharaibeh RZ, Newsome RC et al. 2020. Amending microbiota by targeting intestinal inflammation with TNF blockade attenuates development of colorectal cancer. Nat. Cancer 1:723–34
    [Google Scholar]
  95. 95. 
    Natl. Cancer Inst 2020. Annual Report to the Nation on the Status of Cancer Bethesda, MD: Natl. Cancer Inst https://www.cancer.gov/research/progress/annual-report-nation
  96. 96. 
    Lam KN, Alexander M, Turnbaugh PJ 2019. Precision medicine goes microscopic: engineering the microbiome to improve drug outcomes. Cell Host Microbe 26:122–34
    [Google Scholar]
  97. 97. 
    Maurice CF, Haiser HJ, Turnbaugh PJ 2013. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152:1–239–50
    [Google Scholar]
  98. 98. 
    Geller LT, Barzily-Rokni M, Danino T et al. 2017. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357:63561156–60
    [Google Scholar]
  99. 99. 
    Wallace BD, Wang H, Lane KT et al. 2010. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330:6005831–35
    [Google Scholar]
  100. 100. 
    Bhatt AP, Pellock SJ, Biernat KA et al. 2020. Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy. PNAS 117:137374–81
    [Google Scholar]
  101. 101. 
    Bhatt AP, Redinbo MR, Bultman SJ 2017. The role of the microbiome in cancer development and therapy. CA Cancer J. Clin. 67:4326–44
    [Google Scholar]
  102. 102. 
    Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R et al. 2019. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science 363:6427eaat9931
    [Google Scholar]
  103. 103. 
    Bhatt AP, Grillo L, Redinbo MR 2019. In fimo: a term proposed for excrement examined experimentally. Gastroenterology 156:51232
    [Google Scholar]
  104. 104. 
    He Z, Gharaibeh RZ, Newsome RC et al. 2019. Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin. Gut 68:2289–300
    [Google Scholar]
  105. 105. 
    Rosadi F, Fiorentini C, Fabbri A 2016. Bacterial protein toxins in human cancers. Pathogens Dis 74:1ftv105
    [Google Scholar]
  106. 106. 
    Guidi R, Guerra L, Levi L et al. 2013. Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response. Cell. Microbiol. 15:198–113
    [Google Scholar]
  107. 107. 
    Zhou D, Wang J-D, Weng M-Z et al. 2013. Infections of Helicobacter spp. in the biliary system are associated with biliary tract cancer: a meta-analysis. Eur. J. Gastroenterol. Hepatol. 25:4447–54
    [Google Scholar]
  108. 108. 
    Rao VP, Poutahidis T, Ge Z et al. 2006. Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice. Cancer Res 66:157395–400
    [Google Scholar]
  109. 109. 
    Nagamine CM, Sohn JJ, Rickman BH et al. 2008. Helicobacter hepaticus infection promotes colon tumorigenesis in the BALB/c-Rag2−/−ApcMin/+ mouse. Infect. Immun. 76:62758–66
    [Google Scholar]
  110. 110. 
    Chumduri C, Gurumurthy RK, Zadora PK et al. 2013. Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response. Cell Host Microbe 13:6746–58
    [Google Scholar]
  111. 111. 
    Siegl C, Prusty BK, Karunakaran K et al. 2014. Tumor suppressor p53 alters host cell metabolism to limit Chlamydia trachomatis infection. Cell Rep 9:3918–29
    [Google Scholar]
  112. 112. 
    González E, Rother M, Kerr MC et al. 2014. Chlamydia infection depends on a functional MDM2-p53 axis. Nat. Commun. 5:15201–10
    [Google Scholar]
  113. 113. 
    Caini S, Gandini S, Dudas M et al. 2014. Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis. Cancer Epidemiol 38:4329–38
    [Google Scholar]
  114. 114. 
    Weyler L, Engelbrecht M, Mata Forsberg M et al. 2014. Restriction endonucleases from invasive Neisseria gonorrhoeae cause double-strand breaks and distort mitosis in epithelial cells during infection. PLOS ONE 9:12e114208
    [Google Scholar]
  115. 115. 
    Vielfort K, Söderholm N, Weyler L et al. 2013. Neisseria gonorrhoeae infection causes DNA damage and affects the expression of p21, p27 and p53 in non-tumor epithelial cells. J. Cell. Sci. 126:Pt. 1339–47
    [Google Scholar]
  116. 116. 
    Mughini-Gras L, Schaapveld M, Kramers J et al. 2018. Increased colon cancer risk after severe Salmonella infection. PLOS ONE 13:1e0189721
    [Google Scholar]
  117. 117. 
    Di Domenico EG, Cavallo I, Pontone M et al. 2017. Biofilm producing Salmonella Typhi: chronic colonization and development of gallbladder cancer. Int. J. Mol. Sci. 18:91887
    [Google Scholar]
  118. 118. 
    Martin OCB, Bergonzini A, D'Amico F et al. 2019. Infection with genotoxin-producing Salmonella enterica synergises with loss of the tumour suppressor APC in promoting genomic instability via the PI3K pathway in colonic epithelial cells. Cell Microbiol 21:12e13099
    [Google Scholar]
  119. 119. 
    Won J, Cho Y, Lee D et al. 2019. Clonorchis sinensis excretory-secretory products increase malignant characteristics of cholangiocarcinoma cells in three-dimensional co-culture with biliary ductal plates. PLOS Pathog 15:5e1007818
    [Google Scholar]
  120. 120. 
    Kim T-S, Pak JH, Kim J-B et al. 2016. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review. BMB Rep 49:11590–97
    [Google Scholar]
  121. 121. 
    Arora N, Kaur R, Anjum F et al. 2019. Neglected agent eminent disease: linking human helminthic infection, inflammation, and malignancy. Front. Cell Infect. Microbiol. 9:402
    [Google Scholar]
  122. 122. 
    Tarocchi M, Polvani S, Marroncini G et al. 2014. Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis. World J. Gastroenterol. 20:3311630–40
    [Google Scholar]
  123. 123. 
    Vescovo T, Refolo G, Vitagliano G et al. 2016. Molecular mechanisms of hepatitis C virus-induced hepatocellular carcinoma. Clin. Microbiol. Infect. 22:10853–61
    [Google Scholar]
  124. 124. 
    Wang B, Li X, Liu L et al. 2020. β-Catenin: oncogenic role and therapeutic target in cervical cancer. Biol. Res. 53:133
    [Google Scholar]
  125. 125. 
    Al-Thawadi H, Gupta I, Jabeen A et al. 2020. Co-presence of human papillomaviruses and Epstein-Barr virus is linked with advanced tumor stage: a tissue microarray study in head and neck cancer patients. Cancer Cell Int 20:361
    [Google Scholar]
  126. 126. 
    Yim E-K, Park J-S. 2005. The role of HPV E6 and E7 oncoproteins in HPV-associated cervical carcinogenesis. Cancer Res. Treat. 37:6319–24
    [Google Scholar]
  127. 127. 
    Mohanty S, Harhaj EW. 2020. Mechanisms of oncogenesis by HTLV-1 Tax. Pathogens 9:7543
    [Google Scholar]
  128. 128. 
    Boxus M, Willems L. 2009. Mechanisms of HTLV-1 persistence and transformation. Br. J. Cancer 101:91497–501
    [Google Scholar]
  129. 129. 
    Sripa B, Brindley PJ, Mulvenna J et al. 2012. The tumorigenic liver fluke Opisthorchis viverrini—multiple pathways to cancer. Trends Parasitol 28:10395–407
    [Google Scholar]
  130. 130. 
    Gao S, Li S, Ma Z et al. 2016. Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer. Infect. Agents Cancer 11:13–9
    [Google Scholar]
  131. 131. 
    Malinowski B, Węsierska A, Zalewska K et al. 2019. The role of Tannerella forsythia and Porphyromonas gingivalis in pathogenesis of esophageal cancer. Infect. Agents Cancer 14:13–8
    [Google Scholar]
  132. 132. 
    Nakanishi Y, Wakisaka N, Kondo S et al. 2017. Progression of understanding for the role of Epstein-Barr virus and management of nasopharyngeal carcinoma. Cancer Metastasis Rev 36:3435–47
    [Google Scholar]
  133. 133. 
    Shannon-Lowe C, Rickinson A. 2019. The global landscape of EBV-associated tumors. Front. Oncol. 9:713
    [Google Scholar]
  134. 134. 
    Abere B, Schulz TF. 2016. KSHV non-structural membrane proteins involved in the activation of intracellular signaling pathways and the pathogenesis of Kaposi's sarcoma. Curr. Opin. Virol. 20:11–19
    [Google Scholar]
  135. 135. 
    Broussard G, Damania B. 2019. KSHV: immune modulation and immunotherapy. Front. Immunol. 10:3084
    [Google Scholar]
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