Skip to main content

Advertisement

SpringerLink
Log in

The gastrointestinal microbiota in colorectal cancer cell migration and invasion

  • Review
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Colorectal carcinoma is the third most common cancer in developed countries and the second leading cause of cancer-related mortality. Interest in the influence of the intestinal microbiota on CRC emerged rapidly in the past few years, and the close presence of microbiota to the tumour mass creates a unique microenvironment in CRC. The gastrointestinal microbiota secrete factors that can contribute to CRC metastasis by influencing, for example, epithelial-to-mesenchymal transition. Although the role of EMT in metastasis is well-studied, mechanisms by which gastrointestinal microbiota contribute to the progression of CRC remain poorly understood. In this review, we will explore bacterial factors that contribute to the migration and invasion of colorectal carcinoma and the mechanisms involved. Bacteria involved in the induction of metastasis in primary CRC include Fusobacterium nucleatum, Enterococcus faecalis, enterotoxigenic Bacteroides fragilis, Escherichia coli and Salmonella enterica. Examples of prominent bacterial factors secreted by these bacteria include Fusobacterium adhesin A and Bacteroides fragilis Toxin. Most of these factors induce EMT-like properties in carcinoma cells and, as such, contribute to disease progression by affecting cell-cell adhesion, breakdown of the extracellular matrix and reorganisation of the cytoskeleton. It is of utmost importance to elucidate how bacterial factors promote CRC recurrence and metastasis to increase patient survival. So far, mainly animal models have been used to demonstrate this interplay between the host and microbiota. More human-based models are needed to study the mechanisms that promote migration and invasion and mimic the progression and recurrence of CRC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

APC:

Adenomatous polyposis coli

BFT:

Bacteroides fragilis toxin

CNF1:

Cytotoxic necrotizing factor 1

CRC:

Colorectal cancer

ECM:

Extracellular matrix

EMT:

Epithelial-mesenchymal transition

FGF:

Fibroblast growth factor

GAP:

GTP-ase activating protein

GelE:

Gelatinase E

GPCR:

G-protein coupled receptor

JAM:

Junctional adhesion molecule

LEE:

Locus of enterocyte effacement

MMP:

Matrix metalloproteinase

TGF:

Transforming growth factor

References

  1. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A (2020) Colorectal cancer statistics, 2020. CA Cancer J Clin 70:145–164. https://doi.org/10.3322/caac.21601

    Article  PubMed  Google Scholar 

  2. Dawson H, Lugli A (2015) Molecular and pathogenetic aspects of tumor budding in colorectal cancer. Front Med 2:11. https://doi.org/10.3389/fmed.2015.00011

    Article  Google Scholar 

  3. Schatoff EM, Leach BI, Dow LE (2017) Wnt signaling and colorectal cancer. Curr Color Cancer Rep 13:101–110. https://doi.org/10.1007/s11888-017-0354-9.Wnt

    Article  Google Scholar 

  4. Baran B, Mert Ozupek N, Yerli Tetik N, Acar E, Bekcioglu O, Baskin Y (2018) Difference between left-sided and right-sided colorectal cancer: a focused review of literature. Gastroenterol Res 11:264–273. https://doi.org/10.14740/gr1062w

    Article  CAS  Google Scholar 

  5. Benedix F, Kube R, Meyer F, Schmidt U, Gastinger I, Lippert H (2010) Comparison of 17,641 patients with right- and left-sided colon cancer: Differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum 53:57–64. https://doi.org/10.1007/DCR.0b013e3181c703a4

    Article  PubMed  Google Scholar 

  6. Costi R, Leonardi F, Zanoni D, Violi V, Roncoroni L (2014) Palliative care and end-stage colorectal cancer management: The surgeon meets the oncologist. World J Gastroenterol 20:7602–7621. https://doi.org/10.3748/wjg.v20.i24.7602

    Article  PubMed  PubMed Central  Google Scholar 

  7. Stakelum A, Zaborowski A, Collins D, Winter DC (2019) The influence of the gastrointestinal microbiome on colorectal metastasis: a narrative review. Color Dis.  https://doi.org/10.1111/codi.14930

  8. Santos Ramos F, Wons L, João Cavalli I, Ribeiro MSF (2017) Epithelial-mesenchymal transition in cancer: an overview. Integr Cancer Sci Ther 4:1–5. https://doi.org/10.15761/icst.1000243

    Article  Google Scholar 

  9. Vincan E, Barker N (2008) The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clin Exp Metastasis 25:657–663. https://doi.org/10.1007/s10585-008-9156-4

    Article  CAS  PubMed  Google Scholar 

  10. Tang FY, Pai MH, Chiang EPI (2012) Consumption of high-fat diet induces tumor progression and epithelial-mesenchymal transition of colorectal cancer in a mouse xenograft model. J Nutr Biochem 23:1302–1313. https://doi.org/10.1016/j.jnutbio.2011.07.011

    Article  CAS  PubMed  Google Scholar 

  11. Dinicola S, Masiello MG, Proietti S, Coluccia P, Fabrizi G, Catizone A, Ricci G, de Toma G, Bizzarri M, Cucina A (2018) Nicotine increases colon cancer cell migration and invasion through epithelial to mesenchymal transition (EMT): COX-2 involvement. J Cell Physiol 233:4935–4948. https://doi.org/10.1002/jcp.26323

    Article  CAS  PubMed  Google Scholar 

  12. Zheng K, Yu J, Chen Z, Zhou R, Lin C, Zhang Y, Huang Z, Yu L, Zhao L, Wang Q (2019) Ethanol promotes alcohol-related colorectal cancer metastasis via the TGF-β/RUNX3/Snail axis by inducing TGF-β1 upregulation and RUNX3 cytoplasmic mislocalization. EBioMedicine 50:224–237. https://doi.org/10.1016/j.ebiom.2019.11.011

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gagnière J, Raisch J, Veziant J, Barnich N, Bonnet R, Buc E, Bringer MA, Pezet D, Bonnet M (2016) Gut microbiota imbalance and colorectal cancer. World J Gastroenterol 22:501–518. https://doi.org/10.3748/wjg.v22.i2.501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pretzsch E, Bösch F, Neumann J, Ganschow P, Bazhin A, Guba M, Werner J, Angele M (2019) Mechanisms of metastasis in colorectal cancer and metastatic organotropism: hematogenous versus peritoneal spread. J Oncol. https://doi.org/10.1155/2019/7407190

    Article  PubMed  PubMed Central  Google Scholar 

  15. Casasanta MA, Yoo CC, Udayasuryan B, Sanders BE, Umaña A, Zhang Y, Peng H, Duncan AJ, Wang Y, Li L, Verbridge SS, Slade DJ (2020) Fusobacterium nucleatum host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration. Sci Signal 13:1–30. https://doi.org/10.1126/scisignal.aba9157.Fusobacterium

    Article  Google Scholar 

  16. Wang D, Sun H, Wei J, Cen B, DuBois RN (2017) CXCL1 is critical for pre-metastatic niche formation and metastasis in colorectal cancer. Cancer Res. https://doi.org/10.1016/j.physbeh.2017.03.040

    Article  PubMed  PubMed Central  Google Scholar 

  17. Vu T, Datta PK (2017) Regulation of EMT in colorectal cancer: a culprit in metastasis. Cancers (Basel) 9:1–22. https://doi.org/10.3390/cancers9120171

    Article  CAS  Google Scholar 

  18. Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA (2009) Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest 119:1438–1449. https://doi.org/10.1172/JCI38019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gandalovičová A, Vomastek T, Rosel D, Brábek J (2016) Cell polarity signaling in the plasticity of cancer cell invasiveness. Oncotarget 7:25022–25049. https://doi.org/10.18632/oncotarget.7214

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mowers EE, Sharifi MN, Macleod KF (2017) Autophagy in cancer metastasis. Oncogene 36:1619–1630. https://doi.org/10.1038/onc.2016.333

    Article  CAS  PubMed  Google Scholar 

  21. Junghans D, Haas IG, Kemler R (2005) Mammalian cadherins and protocadherins: About cell death, synapses and processing. Curr Opin Cell Biol 17:446–452. https://doi.org/10.1016/j.ceb.2005.08.008

    Article  CAS  PubMed  Google Scholar 

  22. Yap AS (1998) The morphogenetic role of cadherin cell adhesion molecules in human cancer: a thematic review. Cancer Invest 16:252–261. https://doi.org/10.3109/07357909809039774

    Article  CAS  PubMed  Google Scholar 

  23. Tian X, Liu Z, Niu B, Zhang J, Tan TK, Lee SR, Zhao Y, Harris DCH, Zheng G (2011) E-Cadherin/β-catenin complex and the epithelial barrier. J Biomed Biotechnol. https://doi.org/10.1155/2011/567305

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chen X, Wang Y, Xia H, Wang Q, Jiang X, Lin Z, Ma Y, Yang Y, Hu M (2012) Loss of E-cadherin promotes the growth, invasion and drug resistance of colorectal cancer cells and is associated with liver metastasis. Mol Biol Rep 39:6707–6714. https://doi.org/10.1007/s11033-012-1494-2

    Article  CAS  PubMed  Google Scholar 

  25. Novellasdemunt L, Antas P, Li VSW (2015) Targeting Wnt signaling in colorectal cancer. A review in the theme: cell signaling: proteins, pathways and mechanisms. Am J Physiol - Cell Physiol 309:C511–C521. https://doi.org/10.1152/ajpcell.00117.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lugli A, Zlobec I, Minoo P, Baker K, Tornillo L, Terracciano L, Jass JR (2007) Prognostic significance of the wnt signalling pathway molecules APC, β-catenin and E-cadherin in colorectal cancer - A tissue microarray-based analysis. Histopathology 50:453–464. https://doi.org/10.1111/j.1365-2559.2007.02620.x

    Article  CAS  PubMed  Google Scholar 

  27. Gumbiner B (1987) Structure, biochemistry, and assembly of epithelial tight junctions. Am J Physiol - Cell Physiol. https://doi.org/10.1152/ajpcell.1987.253.6.c749. 253:

    Article  Google Scholar 

  28. Ikenouchi J, Matsuda M, Furuse M, Tsukita S (2003) Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci 116:1959–1967. https://doi.org/10.1242/jcs.00389

    Article  CAS  PubMed  Google Scholar 

  29. Kyuno D, Takasawa A, Kikuchi S, Takemasa I, Osanai M, Kojima T (2021) Role of tight junctions in the epithelial-to-mesenchymal transition of cancer cells. Biochim Biophys Acta - Biomembr 1863:183503. https://doi.org/10.1016/j.bbamem.2020.183503

    Article  CAS  PubMed  Google Scholar 

  30. Wu Y, Zhou BP (2010) TNF-α/NFκ-B/Snail pathway in cancer cell migration and invasion. Br J Cancer 102:639–644. https://doi.org/10.1038/sj.bjc.6605530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bhat A, Pope J, Smith J, Ahmad R, Chen X, Washington M, Beauchamp R, Sing A, Dhawan P (2015) Claudin-7 expression induces mesenchymal to epithelial transformation (MET) to inhibit colon tumorigenesis. Oncogene 34:4570–4580. https://doi.org/10.1038/onc.2014.385

    Article  CAS  PubMed  Google Scholar 

  32. Osanai M, Murata M, Nishikiori N, Chiba H, Kojima T, Sawada N (2006) Epigenetic silencing of occludin promotes tumorigenic and metastatic properties of cancer cells via modulations of unique sets of apoptosis-associated genes. Cancer Res 66:9125–9133. https://doi.org/10.1158/0008-5472.CAN-06-1864

    Article  CAS  PubMed  Google Scholar 

  33. Herszényi L, Hritz I, Lakatos G, Varga MZ, Tulassay Z (2012) The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci 13:13240–13263. https://doi.org/10.3390/ijms131013240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yang B, Tang F, Zhang B, Zhao Y, Feng J, Rao Z (2014) Matrix metalloproteinase-9 overexpression is closely related to poor prognosis in patients with colon cancer. World J Surg Oncol 12:1–6. https://doi.org/10.1186/1477-7819-12-24

    Article  Google Scholar 

  35. Yu S, Zhou R, Yang T, Liu S, Cui Z, Qiao Q, Zhang J (2019) Hypoxia promotes colorectal cancer cell migration and invasion in a SIRT1-dependent manner. Cancer Cell Int 19:1–12. https://doi.org/10.1186/s12935-019-0819-9

    Article  Google Scholar 

  36. Stetler-Stevenson WG (1990) Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev 9:289–303. https://doi.org/10.1007/BF00049520

    Article  CAS  PubMed  Google Scholar 

  37. AznavoorianS Murphy AN, Stetler-Stevenson WG, Liotta LA (1993) Molecular aspects of tumorcell invasion and metastasis. Cancer 71:1368–1383

    Article  Google Scholar 

  38. Toth M, Chvyrkova I, Bernardo MM, Hernandez-Barrantes S, Fridman R (2003) Pro-MMP-9 activation by the MT1-MMP/MMP-2 axis and MMP-3: role of TIMP-2 and plasma membranes. Biochem Biophys Res Commun 308:386–395. https://doi.org/10.1016/S0006-291X(03)01405-0

    Article  CAS  PubMed  Google Scholar 

  39. Dreier R, Grässel S, Fuchs S, Schaumburger J, Bruckner P (2004) Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade. Exp Cell Res 297:303–312. https://doi.org/10.1016/j.yexcr.2004.02.027

    Article  CAS  PubMed  Google Scholar 

  40. Hassan A, Dina Elharouni DH, Hassan Adwan D, Elharouni DH, Banna N, Georges R, Banna N, Georges R, Berger AP MR (2018) Early metastasis in colorectal cancer poses an option for new diagnostic and treatment strategies. Intech Open  https://doi.org/10.1016/j.colsurfa.2011.12.014. 

  41. Mackay AR, Hartzler JL, Pelina MD, Thorgeirsson UP (1990) Studies on the ability of 65-kDa and 92-kDa tumor cell gelatinases to degrade type IV collagen. J Biol Chem 265:21929–21934. https://doi.org/10.1016/s0021-9258(18)45827-9

    Article  CAS  PubMed  Google Scholar 

  42. Beliveau A, Mott JD, Lo A, Chen EI, Koller AA, Yaswen P, Muschler J, Bissell MJ (2010) Raf-induced MMP9 disrupts tissue architecture of human breast cells in three-dimensional culture and is necessary for tumor growth in vivo. Genes Dev 24:2800–2811. https://doi.org/10.1101/gad.1990410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Paolillo M, Schinelli S (2019) Extracellular matrix alterations in metastatic processes. Int J Mol Sci. https://doi.org/10.3390/ijms20194947

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yilmaz M, Christofori G (2009) EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev 28:15–33. https://doi.org/10.1007/s10555-008-9169-0

    Article  PubMed  Google Scholar 

  45. Jiang WG (1995) Focus on science-Membrane ruffling of cancer cells: A parameter of tumour cell motility and invasion. Eur J Surg Oncol 21:307–309. https://doi.org/10.1016/S0748-7983(95)91690-3

    Article  CAS  PubMed  Google Scholar 

  46. Mahankali M, Hong-Juan P, Cox D, Gomez-Cambronero J (2011) The mechanism of cell membrane ruffling relies on a phospholipase D2 (PLD2), GRB2 and RAC2 association. Cell Signal 23:1291–1298. https://doi.org/10.1017/s096719940013014x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Doyle GM, Mohler JL (1992) Prediction of metastatic potential of aspirated cells from the Dunning R-3327 prostatic adenocarcinoma model. J Urol 147:756–759. https://doi.org/10.1016/s0022-5347(17)37373-1

    Article  CAS  PubMed  Google Scholar 

  48. Enomoto T, Asano Y (1994) Induction of membrane ruffling by growth factors in morphologically. Cell Struct Funct 96:89–96

    Article  Google Scholar 

  49. van Larebeke NAF, Bracke ME, Mareel MM (1992) Invasive epithelial cells show more fast plasma membrane movements than related or parental non-invasive cells. Cytometry 13:9–14. https://doi.org/10.1002/cyto.990130104

    Article  PubMed  Google Scholar 

  50. Partin AW, Isaacs JT, Treiger B, Coffey DS (1988) Early cell motility changes associated with an increase in metastatic ability in rat prostatic cancer cells transfected with the v-harvey-ras oncogene. Cancer Res 48:6050–6053

    CAS  PubMed  Google Scholar 

  51. Zientara-Rytter K, Subramani S (2016) Role of actin in shaping autophagosomes. Autophagy 12:2512–2515. https://doi.org/10.1080/15548627.2016.1236877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Morselli E, Galluzzi L, Kepp O, Vicencio JM, Criollo A, Maiuri MC, Kroemer G (2009) Anti- and pro-tumor functions of autophagy. Biochim Biophys Acta - Mol Cell Res 1793:1524–1532. https://doi.org/10.1016/j.bbamcr.2009.01.006

    Article  CAS  Google Scholar 

  53. Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, Codogno P, Debnath J, Gewirtz DA, Karantza V, Kimmelman A, Kumar S, Levine B, Maiuri MC, Martin SJ, Penninger J, Piacentini M, Rubinsztein DC, Simon H, Simonsen A, Thorburn AM, Velasco G, Ryan KM, Kroemer G (2015) Autophagy in malignant transformation and cancer progression. EMBO J 34:856–880. https://doi.org/10.15252/embj.201490784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, Gélinas C, Fan Y, Nelson DA, Jin S, White E (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10:51–64. https://doi.org/10.1016/j.ccr.2006.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, White E (2007) Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 21:1621–1635. https://doi.org/10.1101/gad.1565707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY, Bray K, Reddy A, Bhanot G, Gelinas C, DiPaola RS, Karantza-Wadsworth V, White E (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell 137:1062–1075. https://doi.org/10.1016/j.cell.2009.03.048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Burada F (2015) Autophagy in colorectal cancer: an important switch from physiology to pathology. World J Gastrointest Oncol 7:271. https://doi.org/10.4251/wjgo.v7.i11.271

    Article  PubMed  PubMed Central  Google Scholar 

  58. Sharifi MN, Mowers EE, Drake LE, Collier C, Chen H, Zamora M, Mui S, Macleod KF (2016) Autophagy promotes focal adhesion disassembly and cell motility of metastatic tumor cells through the direct interaction of paxillin with LC3. Cell Rep 15:1660–1672. https://doi.org/10.1016/j.celrep.2016.04.065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sekirov I, Russell SL, Caetano M, Antunes L, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev 90:859–904. https://doi.org/10.1152/physrev.00045.2009

    Article  CAS  PubMed  Google Scholar 

  60. Swidsinski A, Loening-Baucke V, Lochs H, Hale LP (2005) Spatial organization of bacterial flora in normal and inflamed intestine: a fluorescence in situ hybridization study in mice. World J Gastroenterol 11:1131–1140. https://doi.org/10.3748/wjg.v11.i8.1131

    Article  PubMed  PubMed Central  Google Scholar 

  61. Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, Mele MC (2019) What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms. https://doi.org/10.3390/microorganisms7010014

    Article  PubMed  PubMed Central  Google Scholar 

  62. King CH, Desai H, Sylvetsky AC, LoTempio J, Ayanyan S, Carrie J, Crandall KA, Fochtman BC, Gasparyan L, Gulzar N, Howell P, Issa N, Krampis K, Mishra L, Morizono H, Pisegna JR, Rao S, Ren Y, Simonyan V, Smith K, VedBrat S, Yao MD, Mazumder R (2019) Baseline human gut microbiota profile in healthy people and standard reporting template. PLoS ONE 14:1–25. https://doi.org/10.1371/journal.pone.0206484

    Article  CAS  Google Scholar 

  63. Rios-Covian D, Sánchez B, Salazar N, Martínez N, Redruello B, Gueimonde M, de Los Reyes-Gavilán CG (2015) Different metabolic features 1 of Bacteroides fragilis growing in the presence of glucose and exopolysaccharides of bifidobacteria. Front Microbiol 6:1–13. https://doi.org/10.3389/fmicb.2015.00825

    Article  Google Scholar 

  64. Litvak Y, Byndloss MX, Bäumler AJ (2018) Colonocyte metabolism shapes the gut microbiota. Science. https://doi.org/10.1126/science.aat9076

    Article  PubMed  PubMed Central  Google Scholar 

  65. Wang X, Huycke MM (2007) Extracellular superoxide production by enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology 132:551–561. https://doi.org/10.1053/j.gastro.2006.11.040

    Article  CAS  PubMed  Google Scholar 

  66. Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, Jia W, Cai S, Zhao L (2012) Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 6:320–329. https://doi.org/10.1038/ismej.2011.109

    Article  CAS  PubMed  Google Scholar 

  67. Wu Y, Shi L, Li Q, Wu J, Peng W, Li H, Chen K, Ren Y, Fu X (2019) Microbiota diversity in human colorectal cancer tissues is associated with clinicopathological features. Nutr Cancer 71:214–222. https://doi.org/10.1080/01635581.2019.1578394

    Article  CAS  PubMed  Google Scholar 

  68. Tjalsma H, Boleij A, Marchesi JR, Dutilh BE (2012) A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol 10:575–582. https://doi.org/10.1038/nrmicro2819

    Article  CAS  PubMed  Google Scholar 

  69. Sears CL, Pardoll DM (2011) Alpha-bugs, their microbial partners, and the link to colon cancer. J Infect Dis. https://doi.org/10.1093/infdis/jiq061

    Article  PubMed  PubMed Central  Google Scholar 

  70. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Liu C, Shivdasani RA, Ogino S, Tabernero J, Birren BW, Huttenhower C, Garrett WS, Meyerson M (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22(2):292–298. https://doi.org/10.1101/gr.126573.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Repass J, Iorns E, Denis A, Williams SR, Perfito N, Errington TM (2018) Replication study: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Elife 7:299–306. https://doi.org/10.7554/eLife.25801

    Article  Google Scholar 

  72. Marchesi JR, Dutilh BE, Hall N, Peters WHM, Roelofs R, Boleij A, Tjalsma H (2011) Towards the human colorectal cancer microbiome. PLoS ONE. https://doi.org/10.1371/journal.pone.0020447

    Article  PubMed  PubMed Central  Google Scholar 

  73. Lee DH, O’Connor TR, Pfeifer GP (2002) Oxidative DNA damage induced by copper and hydrogen peroxide promotes CG→TT tandem mutations at methylated CpG dinucleotides in nucleotide excision repair-deficient cells. Nucleic Acids Res 30:3566–3573. https://doi.org/10.1093/nar/gkf478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Krakhmal NV, Zavyalova MV, Denisov EV, Vtorushin SV, Perelmuter VM (2015) Cancer invasion: Patterns and mechanisms. Acta Naturae 7:17–28. https://doi.org/10.32607/20758251-2015-7-2-17-28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Singhal R, Shah YM (2020) Oxygen battle in the gut: hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine. J Biol Chem 295:10493–10505. https://doi.org/10.1074/jbc.REV120.011188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Vergara D, Simeone P, Damato M, Maffia M, Lanuti P, Trerotola M (2019) The cancer microbiota: EMT and inflammation as shared molecular mechanisms associated with plasticity and progression. J Oncol. https://doi.org/10.1155/2019/1253727

    Article  PubMed  PubMed Central  Google Scholar 

  77. Bates RC, Mercurio AM (2005) The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther 4:365–370. https://doi.org/10.4161/cbt.4.4.1655

    Article  CAS  PubMed  Google Scholar 

  78. Idrissi Janati A, Karp I, Sabri H, Emami E (2019) Is a Fusobacterium nucleatum infection in the colon a risk factor for colorectal cancer? A systematic review and meta-analysis protocol. Syst Rev 8:4–9. https://doi.org/10.1186/s13643-019-1031-7

    Article  Google Scholar 

  79. Li YY, Ge QX, Cao J, Zhou YJ, Du YL, Shen B, Wan YJY, Nie YQ (2016) Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients. World J Gastroenterol 22:3227–3233. https://doi.org/10.3748/wjg.v22.i11.3227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Yan X, Liu L, Li H, Qin H, Sun Z (2017) Clinical significance of Fusobacterium nucleatum, epithelial–mesenchymal transition, and cancer stem cell markers in stage III /IV colorectal cancer patients. Onco Targets Ther 10:5031–5046. https://doi.org/10.2147/OTT.S145949

    Article  PubMed  PubMed Central  Google Scholar 

  81. Sun Y, An QM, Tian XY, Wang ZL, Guan XY, Dong B, Zhao M, Hao CY (2016) Fusobacterium nucleatum infection is correlated with tumor metastasis and postoperative survival of colorectal cancer patients in China. Transl Cancer Res 5:579–588. https://doi.org/10.21037/tcr.2016.10.45

    Article  CAS  Google Scholar 

  82. Abed J, Maalouf N, Manson AL, Earl AM, Parhi L, Emgård JEM, Klutstein M, Tayeb S, Almogy G, Atlan KA, Chaushu S, Israeli E, Mandelboim O, Garrett WS, Bachrach G (2020) Colon cancer-associated Fusobacterium nucleatum  may originate from the oral cavity and reach colon tumors via the circulatory system. Front Cell Infect Microbiol 10:1–12. https://doi.org/10.3389/fcimb.2020.00400

    Article  CAS  Google Scholar 

  83. Fujiwara N, Kitamura N, Yoshida K, Yamamoto T, Ozaki K, Kudo Y (2020) Involvement of Fusobacterium  species in oral cancer progression: a literature review including other types of cancer. Int J Mol Sci 21:1–10. https://doi.org/10.3390/ijms21176207

    Article  CAS  Google Scholar 

  84. Xu M, Yamada M, Li M, Liu H, Chen SG, Han YW (2007) FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells. J Biol Chem 282:25000–25009. https://doi.org/10.1074/jbc.M611567200

    Article  CAS  PubMed  Google Scholar 

  85. Rubinstein MR, Baik JE, Lagana SM, Han RP, Raab WJ, Sahoo D, Dalerba P, Wang TC, Han YW (2019) Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β-catenin modulator Annexin A1. EMBO Rep 20:1–17. https://doi.org/10.15252/embr.201847638

    Article  CAS  Google Scholar 

  86. Fusté NP, Ferrezuelo F, Garí E (2016) Cyclin D1 promotes tumor cell invasion and metastasis by cytoplasmic mechanisms. Mol Cell Oncol 3:5–7. https://doi.org/10.1080/23723556.2016.1203471

    Article  CAS  Google Scholar 

  87. Li Y, Wei J, Xu C, Zhao Z, You T (2014) Prognostic significance of cyclin D1 expression in colorectal cancer: a meta-analysis of observational studies. PLoS ONE 9:20–25. https://doi.org/10.1371/journal.pone.0094508

    Article  CAS  Google Scholar 

  88. Chen S, Su T, Zhang Y, Lee A, He J, Ge Q, Wang L, Si J, Zhuo W, Wang L (2020) Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating KRT7-AS/KRT7. Gut Microbes 11:511–525. https://doi.org/10.1080/19490976.2019.1695494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lupfer C, Thomas PG, Anand, Paras K, Vogel P, Milasta S, Martinez J, Huang G, Green M, Kundu M, Chi H (2013) Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat Immunol 14:480–488. https://doi.org/10.1038/ni.2563.Receptor

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Chen Y, Chen Y, Zhang J, Cao P, Su W, Deng Y, Zhan N, Fu X, Huang Y, Dong W (2020) Fusobacterium nucleatum promotes metastasis in colorectal cancer by activating autophagy signaling via the upregulation of CARD3 expression. Theranostics 10:323–339. https://doi.org/10.7150/thno.38870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cao P, Chen Y, Chen Y, Su W, Zhan N, Dong W (2020) Fusobacterium nucleatum activates endoplasmic reticulum stress to promote Crohn’s disease development via the upregulation of CARD3 expression. Front Pharmacol 11:1–13. https://doi.org/10.3389/fphar.2020.00106

    Article  CAS  Google Scholar 

  92. de Almeida CV, Taddei A, Amedei A (2018) The controversial role of Enterococcus faecalis in colorectal cancer. Therap Adv Gastroenterol 11:1–11. https://doi.org/10.1177/https

    Article  Google Scholar 

  93. Barnes AMT, Dale JL, Chen Y, Manias DA, Greenwood Quaintance KE, Karau MK, Kashyap PC, Patel R, Wells CL, Dunny GM (2017) Enterococcus faecalis readily colonizes the entire gastrointestinal tract and forms biofilms in a germ-free mouse model. Virulence 8:282–296. https://doi.org/10.1080/21505594.2016.1208890

    Article  CAS  PubMed  Google Scholar 

  94. Zhou Y, He H, Xu H, Li Y, Li Z, Du Y, He J, Zhou Y, Wang H, Nie Y (2016) Association of oncogenic bacteria with colorectal cancer in South China. Oncotarget 7:80794–80802

    Article  PubMed  PubMed Central  Google Scholar 

  95. Sedgley C, Buck G, Appelbe O (2006) Prevalence of Enterococcus faecalis at multiple oral sites in endodontic patients using culture and PCR. J Endod 32:104–109. https://doi.org/10.1016/j.joen.2005.10.022

    Article  PubMed  Google Scholar 

  96. Steck N, Hoffmann M, Sava IG, Kim SC, Hahne H, Tonkonogy SL, Mair K, Krueger D, Pruteanu M, Shanahan F, Vogelmann R, Schemann M, Kuster B, Sartor RB, Haller D (2011) Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology 141:959–971. https://doi.org/10.1053/j.gastro.2011.05.035

    Article  CAS  PubMed  Google Scholar 

  97. Maharshak N, Huh EY, Paiboonrungruang C, Shanahan M, Thurlow L, Herzog J, Djukic Z, Orlando R, Pawlinski R, Ellermann M, Borst L, Patel S, Dotan I, Sartor RB, Carroll IM (2015) Enterococcus faecalis gelatinase mediates intestinal permeability via protease-activated receptor 2. Infect Immun 83:2762–2770. https://doi.org/10.1128/IAI.00425-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Enjoji S, Ohama T, Sato K (2014) Regulation of epithelial cell tight junctions by protease-activated receptor 2. J Vet Med Sci 76:1225–1229. https://doi.org/10.1292/jvms.14-0191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Jacobson RA, Wienholts K, Williamson AJ, Gaines S, Hyoju S, van Goor H, Zaborin A, Shogan BD, Zaborina O, Alverdy JC (2020) Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: Implications in gut healing and identification of druggable targets. Am J Physiol - Gastrointest Liver Physiol 318:G1–G9. https://doi.org/10.1152/AJPGI.00236.2019

    Article  CAS  PubMed  Google Scholar 

  100. Shogan BD, Belogortseva N, Luong PM, Zaborin A, Lax S, Bethel C, Ward M, Muldoon JP, Singer M, An G, Umanskiy K, Konda V, Shakhsheer B, Luo J, Klabbers R, Hancock LE, Gilbert J, Zaborina O, Alverdy JC (2015) Collagen degradation and MMP9 activation by Enterococcus faecalis contributes to intestinal anastomotic leak. Sci Transl Med. https://doi.org/10.1126/scitranslmed.3010658.Collagen

    Article  PubMed  PubMed Central  Google Scholar 

  101. Gaines S, van Praagh JB, Williamson AJ, Jacobson RA, Hyoju S, Zaborin A, Mao J, Koo HY, Alpert L, Bissonnette M, Weichselbaum R, Gilbert J, Chang E, Hyman N, Zaborina O, Shogan BD, Alverdy JC (2020) Western diet promotes intestinal colonization by collagenolytic microbes and promotes tumor formation after colorectal surgery. Gastroenterology 158:958-970e2. https://doi.org/10.1053/j.gastro.2019.10.020

    Article  CAS  PubMed  Google Scholar 

  102. Zamani S, Taslimi R, Sarabi A, Jasemi S, Sechi LA, Feizabadi MM (2020) Enterotoxigenic Bacteroides fragilis: a possible etiological candidate for bacterially-induced colorectal precancerous and cancerous lesions. Front Cell Infect Microbiol 9:1–7. https://doi.org/10.3389/fcimb.2019.00449

    Article  CAS  Google Scholar 

  103. Ignacio A, Fernandes MR, Avila-Campos MJ, Nakano V (2015) Enterotoxigenic and non-enterotoxigenic bacteroides fragilis from fecal microbiota of children. Brazilian J Microbiol 46:1141–1145. https://doi.org/10.1590/S1517-838246420140728

    Article  CAS  Google Scholar 

  104. Haghi F, Goli E, Mirzaei B, Zeighami H (2019) The association between fecal enterotoxigenic B. fragilis with colorectal cancer. BMC Cancer 19:879. https://doi.org/10.1186/s12885-019-6115-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Messaritakis I, Vogiatzoglou K, Tsantaki K, Ntretaki A, Sfakianaki M, Koulouridi A, Tsiaoussis J, Mavroudis D, Souglakos J (2020) The prognostic value of the detection of microbial translocation in the blood of colorectal cancer patients. Cancers (Basel) 12:1–14. https://doi.org/10.3390/cancers12041058

    Article  CAS  Google Scholar 

  106. Huang JY, Lee SM, Mazmanian SK (2011) The human commensal Bacteroides fragilis binds intestinal mucin. Anaerobe 17:137–141. https://doi.org/10.1016/j.anaerobe.2011.05.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Cheng WT, Kantilal HK, Davamani F (2020) The mechanism of Bacteroides fragilis toxin contributes to colon cancer formation. Malaysian J Med Sci 27:9–21. https://doi.org/10.21315/mjms2020.27.4.2

    Article  Google Scholar 

  108. Goodwin AC, Destefano Shields CE, Wu S, Huso DL, Wu XQ, Murray-Stewart TR, Hacker-Prietz A, Rabizadeh S, Woster PM, Sears CL, Casero RA (2011) Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci U S A 108:15354–15359. https://doi.org/10.1073/pnas.1010203108

    Article  PubMed  PubMed Central  Google Scholar 

  109. Saidi RF, Sears CL (1996) Bacteroides fragilis toxin rapidly intoxicates human intestinal epithelial cells (HT29/C1) in vitro. Infect Immun 64:5029–5034. https://doi.org/10.1128/iai.64.12.5029-5034.1996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Wu S, Lim KC, Huang J, Saidi RF, Sears CL (1998) Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. Proc Natl Acad Sci U S A 95:14979–14984. https://doi.org/10.1073/pnas.95.25.14979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Montalban-Arques A, Scharl M (2019) Intestinal microbiota and colorectal carcinoma: implications for pathogenesis, diagnosis, and therapy. EBioMedicine 48:648–655. https://doi.org/10.1016/j.ebiom.2019.09.050

    Article  PubMed  PubMed Central  Google Scholar 

  112. Sun J, Kato I (2016) Gut microbiota, inflammation and colorectal cancer. Genes Dis 3:130–143. https://doi.org/10.1016/j.gendis.2016.03.004

    Article  PubMed  PubMed Central  Google Scholar 

  113. Martin HM, Campbell BJ, Hart CA, Mpofu C, Nayar M, Singh R, Englyst H, Williams HF, Rhodes JM (2004) Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer. Gastroenterology 127:80–93

    Article  CAS  PubMed  Google Scholar 

  114. Tang L, Zhou YJ, Zhu S, Liang G, Da, Zhuang H, Zhao MF, Chang XY, Li HN, Liu Z, Guo ZR, Liu WQ, He X, Wang CX, Zhao DD, Li JJ, Mu XQ, Yao BQ, Li X, Li YG, Duo LB, Wang L, Johnston RN, Zhou J, Zhao JB, Liu GR, Liu SL (2020) E. coli diversity: low in colorectal cancer. BMC Med Genom 13:1–17. https://doi.org/10.1186/s12920-020-0704-3

    Article  Google Scholar 

  115. Desvaux M, Dalmasso G, Beyrouthy R, Barnich N, Delmas J, Bonnet R (2020) Pathogenicity factors of genomic islands in intestinal and extraintestinal Escherichia coli. Front Microbiol. https://doi.org/10.3389/fmicb.2020.02065

    Article  PubMed  PubMed Central  Google Scholar 

  116. Doye A, Mettouchi A, Bossis G, Clément R, Buisson-Touati C, Flatau G, Gagnoux L, Piechaczyk M, Boquet P, Lemichez E (2002) CNF1 exploits the ubiquitin-proteasome machinery to restrict Rho GTPase activation for bacterial host cell invasion. Cell 111:553–564. https://doi.org/10.1016/S0092-8674(02)01132-7

    Article  CAS  PubMed  Google Scholar 

  117. Lee SH, Dominguez R (2010) Regulation of actin cytoskeleton dynamics in cells. Mol Cells 29:311–325. https://doi.org/10.1007/s10059-010-0053-8

    Article  CAS  PubMed  Google Scholar 

  118. Fabbri A, Travaglione S, Fiorentini C (2010) Escherichia coli cytotoxic necrotizing factor 1 (CNF1): toxin biology, in vivo applications and therapeutic potential. Toxins (Basel) 2:283–296. https://doi.org/10.3390/toxins2020282

    Article  CAS  Google Scholar 

  119. Viswanathan VK, Koutsouris A, Lukic S, Pilkinton M, Simonovic I, Simonovic M, Hecht G (2004) Comparative analysis of EspF from enteropathogenic and enterohemorrhagic Escherichia coli in alteration of epithelial barrier function. Infect Immun 72:3218–3227. https://doi.org/10.1128/IAI.72.6.3218-3227.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Bäumler AJ, Tsolis RM, Ficht TA, Adams LG (1998) Evolution of host adaptation in Salmonella enterica. Infect Immun 66:4579–4587. https://doi.org/10.1128/iai.66.10.4579-4587.1998

    Article  PubMed  PubMed Central  Google Scholar 

  121. Ochman H, Groisman EA (1994) The origin and evolution of species differences in Escherichia coli and Salmonella typhimurium. EXS 69:479–493. https://doi.org/10.1007/978-3-0348-7527-1_27

    Article  CAS  PubMed  Google Scholar 

  122. Bulmer DM, Kharraz L, Grant AJ, Dean P, Morgan FJE, Karavolos MH, Doble AC, McGhie EJ, Koronakis V, Daniel RA, Mastroeni P, Anjam Khan CM (2012) The bacterial cytoskeleton modulates motility, type 3 secretion, and colonization in Salmonella. PLoS Pathog 8:13–15. https://doi.org/10.1371/journal.ppat.1002500

    Article  CAS  Google Scholar 

  123. Khan CMA (2014) The dynamic interactions between salmonella and the microbiota, within the challenging niche of the gastrointestinal tract. Int Sch Res Not 2014:1–23. https://doi.org/10.1155/2014/846049

    Article  Google Scholar 

  124. Hardt W-D, Galán JE (1997) A secreted Salmonella protein with homology to an avirulence determinant of plant pathogenic bacteria (bacterial pathogenesis type III secretion host response). Microbiology 94:9887–9892

    CAS  Google Scholar 

  125. Lu R, Wu S, Zhang Y, guo, Xia Y, Zhou Z, Kato I, Dong H, Bissonnette M, Sun J (2016) Salmonella protein AvrA Activates the STAT3 signaling pathway in colon cancer. Neoplasia 18:307–316. https://doi.org/10.1016/j.neo.2016.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Gaytán MO, Martínez-Santos VI, Soto E, González-Pedrajo B (2016) Type three secretion system in attaching and effacing pathogens. Front Cell Infect Microbiol 6:1–25. https://doi.org/10.3389/fcimb.2016.00129

    Article  CAS  Google Scholar 

  127. Lu R, Wu S, Zhang YG, Xia Y, Liu X, Zheng Y, Chen H, Schaefer KL, Zhou Z, Bissonnette M, Li L, Sun J (2014) Enteric bacterial protein AvrA promotes colonic tumorigenesis and activates colonic beta-catenin signaling pathway. Oncogenesis 3:1–10. https://doi.org/10.1038/oncsis.2014.20

    Article  CAS  Google Scholar 

  128. Liu X, Lu R, Wu S, Sun J (2010) Salmonella regulation of intestinal stem cells through the Wnt/β-catenin pathway. FEBS Lett 584:911–916. https://doi.org/10.1016/j.febslet.2010.01.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Ye Z, Petrof EO, Boone D, Claud EC, Sun J (2007) Salmonella effector AvrA regulation of colonic epithelial cell inflammation by deubiquitination. Am J Pathol 171:882–892. https://doi.org/10.2353/ajpath.2007.070220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Lu R, Bosland M, Xia Y, Zhang Y, Kato I, Kato, Lu R, Sun J (2017) Presence of Salmonella AvrA in colorectal tumor and its precursor lesions in mouse intestine and human specimens. Oncotarget 8:55104–55115

    Article  PubMed  PubMed Central  Google Scholar 

  131. Faïs T, Delmas J, Cougnoux A, Dalmasso G, Bonnet R (2016) Targeting colorectal cancer-associated bacteria: a new area of research for personalized treatments. Gut Microbes 7:329–333. https://doi.org/10.1080/19490976.2016.1155020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, Geller LT, Rotter-Maskowitz A, Weiser R, Mallel G, Gigi E, Meltser A, Douglas GM, Kamer I, Gopalakrishnan V, Dadosh T, Levin-Zaidman S, Avnet S, Atlan T, Cooper ZA, Arora R, Cogdill AP, Khan MAW, Ologun G, Bussi Y, Weinberger A, Lotan-Pompan M, Golani O, Perry G, Rokah M, Bahar-Shany K, Rozeman EA, Blank CU, Ronai A, Shaoul R, Amit A, Dorfman T, Kremer R, Cohen ZR, Harnof S, Siegal T, Yehuda-Shnaidman E, Gal-Yam EN, Shapira H, Baldini N, Langille MGI, Ben-Nun A, Kaufman B, Nissan A, Golan T, Dadiani M, Levanon K, Bar J, Yust SK, Barshack I, Peeper DS, Raz DJ, Segal E, Wargo JA, Sandbank J, Shental N, Straussman R (2020) The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science (80-) 368:973–980. https://doi.org/10.1126/science.aay9189

    Article  CAS  Google Scholar 

  133. Qiu H, Sun X, Sun M, He C, Li Z, Liu Z (2014) Serum bacterial toxins are related to the progression of inflammatory bowel disease. Scand J Gastroenterol 49:826–833. https://doi.org/10.3109/00365521.2014.919018

    Article  CAS  PubMed  Google Scholar 

  134. Cox SR, Lindsay JO, Fromentin S, Stagg AJ, McCarthy NE, Galleron N, Ibraim SB, Roume H, Levenez F, Pons N, Maziers N, Lomer MC, Ehrlich SD, Irving PM, Whelan K (2020) Effects of low FODMAP diet on symptoms, fecal microbiome, and markers of inflammation in patients with quiescent inflammatory bowel disease in a randomized trial. Gastroenterology 158:176-188e7. https://doi.org/10.1053/j.gastro.2019.09.024

    Article  CAS  PubMed  Google Scholar 

  135. Mendonça LABM, Ferreira R, dos Guimarães S, de CA R, de Castro AP, Franco OL, Matias R, Carvalho CME (2018) The complex puzzle of interactions among functional food, gut microbiota, and colorectal cancer. Front Oncol 8:1–10. https://doi.org/10.3389/fonc.2018.00325

    Article  Google Scholar 

  136. Vipperla K, O’Keefe SJ (2016) Diet, microbiota, and dysbiosis: a “recipe” for colorectal cancer. Food Funct 7:1731–1740. https://doi.org/10.1039/c5fo01276g

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Lawley TD, Walker AW (2013) Intestinal colonization resistance. Immunology 138:1–11. https://doi.org/10.1111/j.1365-2567.2012.03616.x

    Article  CAS  PubMed  Google Scholar 

  138. Liu Q, Yu Z, Tian F, Zhao J, Zhang H, Zhai Q, Chen W (2020) Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier. Microb Cell Fact 19:1–11. https://doi.org/10.1186/s12934-020-1289-4

    Article  CAS  Google Scholar 

  139. Martin TA, Jiang WG (2009) Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta  1788:872–891. https://doi.org/10.1016/j.bbamem.2008.11.005

    Article  CAS  PubMed  Google Scholar 

  140. Park R, Umar S, Kasi A (2020) Immunotherapy in colorectal cancer: potential of fecal transplant and microbiota-augmented clinical trials. Curr Colorectal Cancer Rep 16:81–88. https://doi.org/10.1007/s11888-020-00456-1

    Article  PubMed  PubMed Central  Google Scholar 

  141. Crook N, Ferreiro A, Gasparrini AJ, Pesesky MW, Gibson MK, Wang B, Sun X, Condiotte Z, Dobrowolski S, Peterson D, Dantas G (2019) Adaptive strategies of the candidate probiotic E. coli nissle in the mammalian gut. Cell Host Microbe 25:499-512e8. https://doi.org/10.1016/j.chom.2019.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Sivamaruthi BS, Kesika P, Chaiyasut C (2020) The role of probiotics in colorectal cancer management. Evidence-Based Complement Altern Med.  https://doi.org/10.1155/2020/3535982. 

  143. Liu Y, Tran DQ, Rhoads JM (2018) Probiotics in disease prevention and treatment. J Clin Pharmacol 58:S164–S179. https://doi.org/10.1002/jcph.1121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon S, Fasani R, Aguirre AJ, Ng K, Élez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M (2017) Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science (80-) 358:1443–1448. https://doi.org/10.1126/science.aal5240

    Article  CAS  Google Scholar 

  145. Lu L, Zhuang T, Shao E, Liu Y, He H, Shu Z, Huang Y, Yao Y, Lin S, Lin S, Chen X, Chen X (2019) Association of antibiotic exposure with the mortality in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy: a hospital-based retrospective cohort study. PLoS ONE 14:1–11. https://doi.org/10.1371/journal.pone.0221964

    Article  CAS  Google Scholar 

  146. Abdel-Rahman O, Ghosh S, Walker J (2020) Outcomes of metastatic colorectal cancer patients in relationship to prior and concurrent antibiotics use; individual patient data analysis of three clinical trials. Clin Transl Oncol 22:1651–1656. https://doi.org/10.1007/s12094-020-02301-1

    Article  CAS  PubMed  Google Scholar 

  147. Murota Y, Jobin C (2021) Bacteria break barrier to promote metastasis. Cancer Cell 39:598–600. https://doi.org/10.1016/j.ccell.2021.03.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Bertocchi A, Carloni S, Ravenda PS, Bertalot G, Spadoni I, Lo Cascio A, Gandini S, Lizier M, Braga D, Asnicar F, Segata N, Klaver C, Brescia P, Rossi E, Anselmo A, Guglietta S, Maroli A, Spaggiari P, Tarazona N, Cervantes A, Marsoni S, Lazzari L, Jodice MG, Luise C, Erreni M, Pece S, Di Fiore PP, Viale G, Spinelli A, Pozzi C, Penna G, Rescigno M (2021) Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell 39:708–724e11. https://doi.org/10.1016/j.ccell.2021.03.004

    Article  CAS  PubMed  Google Scholar 

  149. Mao J, Zaborin A, Poroyko V, Goldfeld D, Lynd NA, Chen W, Tirrell MV, Zaborina O, Alverdy JC (2017) De novo synthesis of phosphorylated triblock copolymers with pathogen virulence-suppressing properties that prevent infection-related mortality. ACS Biomater Sci Eng 3:2076–2085. https://doi.org/10.1021/acsbiomaterials.7b00373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Sedighi M, Zahedi Bialvaei A, Hamblin MR, Ohadi E, Asadi A, Halajzadeh M, Lohrasbi V, Mohammadzadeh N, Amiriani T, Krutova M, Amini A, Kouhsari E (2019) Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities. Cancer Med 8:3167–3181. https://doi.org/10.1002/cam4.2148

    Article  PubMed  PubMed Central  Google Scholar 

  151. Ellegaard KM, Engel P (2016) Beyond 16S rRNA community profiling: intra-species diversity in the gut microbiota. Front Microbiol 7:1–16. https://doi.org/10.3389/fmicb.2016.01475

    Article  Google Scholar 

  152. Kostic AD, Howitt MR, Garrett WS (2013) Exploring host-microbiota interactions in animal models and humans. Genes Dev 27:701–718. https://doi.org/10.1101/gad.212522.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Santos Adel-Sayed and BioRender for graphical support and inspiration for the figures of this manuscript. CH is supported by a PhD scholarship from the Molecular Life and Health Program of the University of Groningen.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands

    Charlotte Henstra & Anika Nagelkerke

  2. Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands

    Charlotte Henstra & Peter Olinga

  3. Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

    Jasper van Praagh

Authors
  1. Charlotte Henstra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jasper van Praagh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Olinga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anika Nagelkerke
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: all authors. Literature search: CH. Analysis and interpretation of data: all authors. Manuscript writing and editing: all authors. Approval of final article: all authors.

Corresponding author

Correspondence to Anika Nagelkerke.

Ethics declarations

Conflicts of interest The authors have no relevant financial or non-financial interests to disclose

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Henstra, C., van Praagh, J., Olinga, P. et al. The gastrointestinal microbiota in colorectal cancer cell migration and invasion. Clin Exp Metastasis 38, 495–510 (2021). https://doi.org/10.1007/s10585-021-10130-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-021-10130-x

Keywords

Search

Navigation