The role of cancer stem cells in pathogenesis of colorectal cancer
Magdalena Szaryńska 1 , Agata Olejniczak 1 , Zbigniew Kmieć 1Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer, accounting for about 10% of total adult malignancies worldwide. The majority of CRC cases are diagnosed at the late stage; thus the investigation of the pathogenesis of early-stage disease and its detection could prevent formation of metastasis, a leading cause of death. This review highlights the recent progress in the understanding of the development of cancer stem cells (CSCs) in the colon epithelium and mechanisms of their proliferation. Moreover, we describe the role of the CSCs in resistance to chemotherapy and formation of metastases. We present evidence for the importance of the interactions between CSCs and their environment in the propagation of the disease. It is hoped that further studies of colorectal cancer CSCs could be helpful in the early detection and improved therapy of this neoplasm.
References
- 1. Ashktorab H., Schäffer A.A., Daremipouran M., Smoot D.T., LeeE., Brim H.: Distinct genetic alterations in colorectal cancer. PLoSOne, 2010; 5: e8879
Google Scholar - 2. Balmana J., Stockwell D.H., Steyerberg E.W., Stoffel E.M., DeffenbaughA.M., Reid J.E., Ward B., Scholl T., Hendrickson B., Tazelaar J.,Burbidge L.A., Syngal S.: Prediction of MLH1 and MSH2 mutationsin Lynch syndrome. JAMA, 2006; 296: 1469-1478
Google Scholar - 3. Barker N., Ridgway R.A., van Es J.H., van de Wetering M., BegthelH., van den Born M., Danenberg E., Clarke A.R., Sansom O.J., CleversH.: Crypt stem cells as the cells-of-origin of intestinal cancer. Nature,2009; 457: 608-611
Google Scholar - 4. Barker N., van Es J.H., Kuipers J., Kujala P., van den Born M., CozijnsenM., Haegebarth A., Korving J., Begthel H., Peters P.J., CleversH.: Identification of stem cells in small intestine and colon by markergene Lgr5. Nature, 2007; 449: 1003-1007
Google Scholar - 5. Barnetson R.A., Tenesa A., Farrington S.M., Nicholl I.D., CetnarskyjR., Porteous M.E., Campbell H., Dunlop M.G.: Identification andsurvival of carriers of mutations in DNA mismatch-repair genes incolon cancer. N. Engl. J. Med., 2006; 354: 2751-2763 6 Bartel D.P.: MicroRNAs: genomics, biogenesis, mechanism, andfunction. Cell, 2004; 116: 281-297
Google Scholar - 6. in patients with colorectal cancer. Saudi J. Gastroenterol.,2011; 17: 170-173
Google Scholar - 7. Becker C., Fantini M.C., Schramm C., Lehr H.A., Wirtz S., NikolaevA., Burg J., Strand S., Kiesslich R., Huber S., Ito H., NishimotoN., Yoshizaki K., Kishimoto T., Galle P.R., Blessing M., Rose-John S.,Neurath M.F.: TGF-β suppresses tumor progression in colon cancerby inhibition of IL-6 trans-signaling. Immunity, 2004; 21: 491-501
Google Scholar - 8. Becker C., Fantini M.C., Wirtz S., Nikolaev A., Lehr H.A., Galle P.R.,Rose-John S., Neurath M.F.: IL-6 signaling promotes tumor growthin colorectal cancer. Cell Cycle, 2005; 4: 217-220
Google Scholar - 9. Bellis J., Duluc I., Romagnolo B., Perret C., Faux M.C., Dujardin D.,Formstone C., Lightowler S., Ramsay R.G., Freund J.N., De Mey J.R.:The tumor suppressor Apc controls planar cell polarities central togut homeostasis. J. Cell Biol., 2012; 198: 331-341
Google Scholar - 10. Belluco C., Olivieri F., Bonafe M., Giovagnetti S., Mammano E.,Scalerta R., Ambrosi A., Franceschi C., Nitti D., Lise M.: -174 G>Cpolymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin. Cancer Res.,2003; 9: 2173-2176
Google Scholar - 11. Bettington M., Walker N., Clouston A., Brown I., Leggett B.,Whitehall V.: The serrated pathway to colorectal carcinoma: currentconcepts and challenges. Histopathology, 2013; 62: 367-386
Google Scholar - 12. Bonasio R., Tu S., Reinberg D.: Molecular signals of epigeneticstates. Science, 2010; 330: 612-616
Google Scholar - 13. Botchkina I.L., Rowehl R.A., Rivadeneira D.E., Karpeh M.S.Jr.,Crawford H., Dufour A., Ju J., Wang Y., Leyfman Y., Botchkina G.I.:Phenotypic subpopulations of metastatic colon cancer stem cells:genomic analysis. Cancer Genomics Proteomics, 2009; 6: 19-29
Google Scholar - 14. Brenner H., Kloor M., Pox C.P.: Colorectal cancer. Lancet, 2014;383: 1490-1502
Google Scholar - 15. Brozek W., Bises G., Fabjani G., Cross H.S., Peterlik M.: Clonespecificexpression, transcriptional regulation, and action of interleukin- 6 in human colon carcinoma cells. BMC Cancer, 2008; 8: 13
Google Scholar - 16. Brozek W., Bises G., Girsch T., Cross H.S., Kaiser H.E., PeterlikM.: Differentiation-dependent expression and mitogenic action ofinterleukin-6 in human colon carcinoma cells: relevance for tumourprogression. Eur. J. Cancer, 2005; 41: 2347-2354
Google Scholar - 17. Buczacki S.J., Zecchini H.I., Nicholson A.M., Russell R., VermeulenL., Kemp R., Winton D.J.: Intestinal label-retaining cells are secretoryprecursors expressing Lgr5. Nature, 2013; 495: 65-69
Google Scholar - 18. Chalitchagorn K., Shuangshoti S., Hourpai N., KongruttanachokN., Tangkijvanich P., Thong-ngam D., Voravud N., Sriuranpong V.,Mutirangura A.: Distinctive pattern of LINE-1 methylation level innormal tissues and the association with carcinogenesis. Oncogene,2004; 23: 8841-8846
Google Scholar - 19. Cheah M.S., Wallace C.D., Hoffman R.M.: Hypomethylation ofDNA in human cancer cells: a site-specific change in the c-myc oncogene.J. Natl. Cancer Inst., 1984; 73: 1057-1065
Google Scholar - 20. Chen J., Röcken C., Lofton-Day C., Schulz H.U., Müller O., KutznerN., Malfertheiner P., Ebert M.P.: Molecular analysis of APC promotermethylation and protein expression in colorectal cancer metastasis.Carcinogenesis, 2005; 26: 37-43
Google Scholar - 21. Chowdhury S., Howell G.M., Rajput A., Teggart C.A., Brattain L.E.,Weber H.R., Chowdhury A., Brattain M.G.: Identification of a novelTGFβ/PKA signaling transduceome in mediating control of cellsurvival and metastasis in colon cancer. PLoS One, 2011; 6: e19335
Google Scholar - 22. Clevers H.: The intestinal crypt, a prototype stem cell compartment.Cell, 2013; 154: 274-284
Google Scholar - 23. Cui H., Horon I.L., Ohlsson R., Hamilton S.R., Feinberg A.P.: Lossof imprinting in normal tissue of colorectal cancer patients withmicrosatellite instability. Nat. Med., 1998; 4: 1276-1280
Google Scholar - 24. Dalerba P., Dylla S.J., Park I.K., Liu R., Wang X., Cho R.W., Hoey T.,Gurney A., Huang E.H., Simeone D.M., Shelton A.A., Parmiani G., CastelliC., Clarke M.F.: Phenotypic characterization of human colorectalcancer stem cells. Proc. Natl. Acad. Sci. USA, 2007; 104: 10158-10163
Google Scholar - 25. de Lau W., Barker N., Low T.Y., Koo B.K., Li V.S., Teunissen H.,Kujala P., Haegebarth A., Peters P.J., van de Wetering M., Stange D.E.,van Es J.E., Guardavaccaro D., Schasfoort R.B., Mohri Y., NishimoriK., Mohammed S., Heck A.J., Clevers H.: Lgr5 homologues associatewith Wnt receptors and mediate R-spondin signalling. Nature,2011; 476: 293-297
Google Scholar - 26. De Mey J.R., Freund J.N.: Understanding epithelial homeostasisin the intestine: an old battlefield of ideas, recent breakthroughs andremaining controversies. Tissue Barriers, 2013; 1: e24965
Google Scholar - 27. Ebert M.P., Mooney S.H., Tonnes-Priddy L., Lograsso J., HoffmannJ., Chen J., Röcken C., Schulz H.U., Malfertheiner P., Lofton-Day C.:Hypermethylation of the TPEF/HPP1 gene in primary and metastaticcolorectal cancers. Neoplasia, 2005; 7: 771-778
Google Scholar - 28. Eldesoky A., Shouma A., Mosaad Y., Elhawary A.: Clinical relevanceof serum vascular endothelial growth factor and interleukin-
Google Scholar - 29. Erez N., Truitt M., Olson P., Arron S.T., Hanahan D.: Cancer-associatedfibroblasts are activated in incipient neoplasia to orchestratetumor-promoting inflammation in an NF-κB-dependent manner.Cancer Cell, 2010; 17: 135-147
Google Scholar - 30. Escobar M., Nicolas P., Sangar F., Laurent-Chabalier S., Clair P.,Joubert D., Jay P., Legraverend C.: Intestinal epithelial stem cells donot protect their genome by asymmetric chromosome segregation.Nat. Commun., 2011; 2: 258
Google Scholar - 31. Fábián A., Barok M., Vereb G., Szöllosi J.: Die hard: are cancerstem cells the Bruce Willises of tumor biology? Cytometry A, 2009;75: 67-74
Google Scholar - 32. Fafilek B., Krausova M., Vojtechova M., Pospichalova V., TumovaL., Sloncova E., Huranova M., Stancikova J., Hlavata A., Svec J., SedlacekR., Luksan O., Oliverius M., Voska L., Jirsa M., Paces J., KolarM., Krivjanska M., Klimesova K., Tlaskalova-Hogenova H., KorinekV.: Troy, a tumor necrosis factor receptor family member, interactswith lgr5 to inhibit wnt signaling in intestinal stem cells. Gastroenterology,2013; 144: 381-391
Google Scholar - 33. Fearon E.R., Vogelstein B.: A genetic model for colorectal tumorigenesis.Cell, 1990; 61: 759-767
Google Scholar - 34. Francipane M.G., Alea M.P., Lombardo Y., Todaro M., MedemaJ.P., Stassi G.: Crucial role of interleukin-4 in the survival of coloncancer stem cells. Cancer Res., 2008; 68: 4022-4025
Google Scholar - 35. Furuyama K., Kawaguchi Y., Akiyama H., Horiguchi M., KodamaS., Kuhara T., Hosokawa S., Elbahrawy A., Soeda T., Koizumi M., MasuiT., Kawaguchi M., Takaori K., Doi R., Nishi E. i wsp.: Continuous cellsupply from a Sox9-expressing progenitor zone in adult liver, exocrinepancreas and intestine. Nat. Genet, 2011; 43: 34-41
Google Scholar - 36. Gândara R.M., Mahida Y.R., Potten C.S.: Regional differences instem and transit cell proliferation and apoptosis in the terminal ileumand colon of mice after 12 Gy. Int. J. Radiat. Oncol. Biol. Phys.,2012; 82: e521-528
Google Scholar - 37. Goelz S.E., Vogelstein B., Hamilton S.R., Feinberg A.P.: Hypomethylationof DNA from benign and malignant human colon neoplasms.Science, 1985; 228: 187-190
Google Scholar - 38. Goto T., Mizukami H., Shirahata A., Sakata M., Saito M., IshibashiK., Kigawa G., Nemoto H., Sanada Y., Hibi K.: Aberrant methylation ofthe p16 gene is frequently detected in advanced colorectal cancer.Anticancer Res., 2009; 29: 275-277
Google Scholar - 39. Gregorieff A., Stange D.E., Kujala P., Begthel H., van den BornM., Korving J., Peters P.J., Clevers H.: The ets-domain transcriptionfactor Spdef promotes maturation of goblet and paneth cells in theintestinal epithelium. Gastroenterology, 2009; 137: 1333-1345
Google Scholar - 40. Hanahan D., Weinberg R.A.: The hallmarks of cancer. Cell, 2000;100: 57-70
Google Scholar - 41. Haraguchi N., Ohkuma M., Sakashita H., Matsuzaki S., TanakaF., Mimori K., Kamohara Y., Inoue H., Mori M.: CD133+CD44+ populationefficiently enriches colon cancer initiating cells. Ann. Surg.Oncol., 2008; 15: 2927-2933
Google Scholar - 42. Hsu C.P., Chung Y.C.: Influence of interleukin-6 on the invasivenessof human colorectal carcinoma. Anticancer Res., 2006; 26:4607-4614
Google Scholar - 43. Hu J.J., Wang Z.T., Zhong J.: Lack of association between theinterleukin 6 gene -174G>C polymorphism and colorectal cancer:evidence from a meta-analysis. Genet. Mol. Res., 2013: 12: 2205-2214
Google Scholar - 44. Huang E.H., Hynes M.J., Zhang T., Ginestier C., Dontu G., AppelmanH., Fields J.Z., Wicha M.S., Boman B.M.: Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stemcells (SC) and tracks SC overpopulation during colon tumorigenesis.Cancer Res., 2009; 69: 3382-3389
Google Scholar - 45. Huang W.H., Chang M.C., Tsai K.S., Hung M.C., Chen H.L., HungS.C.: Mesenchymal stem cells promote growth and angiogenesis oftumors in mice. Oncogene, 2013; 32: 4343-4354
Google Scholar - 46. Isoda T., Nakatsu Y., Yamauchi K., Piao J., Yao T., Honda H., NakabeppuY., Tsuzuki T.: Abnormality in Wnt signaling is causativelyassociated with oxidative stress-induced intestinal tumorigenesisin MUTYH-null mice. Int. J. Biol. Sci., 2014; 10: 940-947
Google Scholar - 47. Itzkovitz S., Blat I.C., Jacks T., Clevers H., van Oudenaarden A.:Optimality in the development of intestinal crypts. Cell, 2012; 148:608-619
Google Scholar - 48. Jass J.R.: Classification of colorectal cancer based on correlationof clinical, morphological and molecular features. Histopathology,2007; 50: 113-130
Google Scholar - 49. King J.B., von Furstenberg R.J., Smith B.J., McNaughton K.K.,Galanko J.A., Henning S.J.: CD24 can be used to isolate Lgr5+ putativecolonic epithelial stem cells in mice. Am. J. Physiol. Gastrointest.Liver Physiol., 2012; 303: G443-G452
Google Scholar - 50. Knüpfer H., Preiss R.: Serum interleukin-6 levels in colorectalcancer patients – a summary of published results. Int. J. Colorectal.Dis., 2010; 25: 135-140
Google Scholar - 51. Krausova M., Korinek V.: Wnt signaling in adult intestinal stemcells and cancer. Cell Signal., 2014; 26: 570-579
Google Scholar - 52. Lapidot T., Sirard C., Vormoor J., Murdoch B., Hoang T., Caceres-Cortes J., Minden M., Paterson B., Caligiuri M.A., Dick J.E.: A cellinitiating human acute myeloid leukaemia after transplantationinto SCID mice. Nature, 1994; 367: 645-648
Google Scholar - 53. Leedham S.J.: Measuring stem cell dynamics in the human colon- where there›s a wiggle, there›s a way. J. Pathol., 2014; 234: 292-295
Google Scholar - 54. Li Q., Chen H.: Transcriptional silencing of N-Myc downstream-regulated gene 1 (NDRG1) in metastatic colon cancer cell lineSW620. Clin. Exp. Metastasis, 2011; 28: 127-135
Google Scholar - 55. Liu Y., Han Z.P., Zhang S.S., Jing Y.Y., Bu X.X., Wang C.Y., Sun K.,Jiang G.C., Zhao X., Li R., Gao L., Zhao Q.D., Wu M.C., Wei L.X.: Effectsof inflammatory factors on mesenchymal stem cells and their role inthe promotion of tumor angiogenesis in colon cancer. J. Biol. Chem.,2011; 286: 25007-25015
Google Scholar - 56. Lynch H.T., de la Chapelle A.: Hereditary colorectal cancer. N.Engl. J. Med., 2003; 348: 919-932
Google Scholar - 57. Magney J.E., Erlandsen S.L., Bjerknes M.L., Cheng H.: Scanningelectron microscopy of isolated epithelium of the murine gastrointestinaltract: morphology of the basal surface and evidence forparacrinelike cells. Am. J. Anat., 1986; 177: 43-53
Google Scholar - 58. Marshman E., Booth C., Potten C.S.: The intestinal epithelialstem cell. Bioessays, 2002; 24: 91-98
Google Scholar - 59. Mathonnet M., Perraud A., Christou N., Akil H., Melin C., BattuS., Jauberteau M.O., Denizot Y.: Hallmarks in colorectal cancer: angiogenesisand cancer stem-like cells. World J. Gastroenterol., 2014;20: 4189-4196
Google Scholar - 60. May R., Riehl T.E., Hunt C., Sureban S.M., Anant S., HouchenC.W.: Identification of a novel putative gastrointestinal stem cell andadenoma stem cell marker, doublecortin and CaM kinase-like-1, followingradiation injury and in adenomatous polyposis coli/multipleintestinal neoplasia mice. Stem Cells, 2008; 26: 630-637
Google Scholar - 61. Medema J.P., Vermeulen L.: Microenvironmental regulationof stem cells in intestinal homeostasis and cancer. Nature, 2011;474: 318-326
Google Scholar - 62. Mehlen P., Fearon E.R.: Role of the dependence receptor DCC incolorectal cancer pathogenesis. J. Clin. Oncol., 2004; 22: 3420-3428
Google Scholar - 63. Menendez J.A., Joven J., Cufi S., Corominas-Faja B., Oliveras-Ferraros C., Cuyas E., Martin-Castillo B., López-Bonet E., AlarcónT., Vazquez-Martin A.: The Warburg effect version 2.0: metabolicreprogramming of cancer stem cells. Cell Cycle, 2013; 12: 1166-1179
Google Scholar - 64. Metcalfe C., Kljavin N.M., Ybarra R., de Sauvage F.J.: Lgr5+ stemcells are indispensable for radiation-induced intestinal regeneration.Cell Stem Cell, 2014; 14: 149-159
Google Scholar - 65. Mishra P.J., Mishra P.J., Humeniuk R., Medina D.J., Alexe G., MesirovJ.P., Ganesan S., Glod J.W., Banerjee D.: Carcinoma-associatedfibroblast-like differentiation of human mesenchymal stem cells.Cancer Res., 2008; 68: 4331-4339
Google Scholar - 66. Montgomery R.K., Carlone D.L., Richmond C.A., Farilla L.,Kranendonk M.E., Henderson D.E., Baffour-Awuah N.Y., AmbruzsD.M., Fogli L.K., Algra S., Breault D.T.: Mouse telomerase reversetranscriptase (mTert) expression marks slowly cycling intestinalstem cells. Proc. Natl. Acad.Sci. USA, 2011; 108: 179-184
Google Scholar - 67. Nishimura S., Wakabayashi N., Toyoda K., Kashima K., MitsufujiS.: Expression of Musashi-1 in human normal colon crypt cells:a possible stem cell marker of human colon epithelium. Dig. Dis.Sci., 2003; 48: 1523-1529
Google Scholar - 68. O›Brien C.A., Pollett A., Gallinger S., Dick J.E.: A human coloncancer cell capable of initiating tumour growth in immunodeficientmice. Nature, 2007; 445: 106-110
Google Scholar - 69. Paldino E., Tesori V., Casalbore P., Gasbarrini A., Puglisi M.A.: Tumorinitiating cells and chemoresistance: which is the best strategyto target colon cancer stem cells? Biomed. Res. Int., 2014; 2014: 859871
Google Scholar - 70. Pancione M., Giordano G., Remo A., Febbraro A., Sabatino L.,Manfrin E., Ceccarelli M., Colantuoni V.: Immune escape mechanismsin colorectal cancer pathogenesis and liver metastasis. J. Immunol.Res., 2014; 2014: 686879
Google Scholar - 71. Potten C.S.: Extreme sensitivity of some intestinal crypt cells toX and gamma irradiation. Nature, 1977; 269: 518-521
Google Scholar - 72. Potten C.S.: Stem cells in gastrointestinal epithelium: numbers,characteristics and death. Philos. Trans R. Soc. Lond. B Biol. Sci.,1998; 353: 821-830
Google Scholar - 73. Potten C.S., Loeffler M.: A comprehensive model of the cryptsof the small intestine of the mouse provides insight into the mechanismsof cell migration and the proliferation hierarchy. J. Theor.Biol., 1987; 127: 381-391
Google Scholar - 74. Potten C.S., Owen G., Booth D.: Intestinal stem cells protecttheir genome by selective segregation of template DNA strands. J.Cell Sci., 2002; 115: 2381-2388
Google Scholar - 75. Powell A.E., Wang Y., Li Y., Poulin E.J., Means A.L., WashingtonM.K., Higginbotham J.N., Juchheim A., Prasad N., Levy S.E., Guo Y.,Shyr Y., Aronow B.J., Haigis K.M., Franklin J.L., Coffey R.J.: The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker thatfunctions as a tumor suppressor. Cell, 2012; 149: 146-158
Google Scholar - 76. Raver-Shapira N., Marciano E., Meiri E., Spector Y., RosenfeldN., Moskovits N., Bentwich Z., Oren M.: Transcriptional activationof miR-34a contributes to p53-mediated apoptosis. Mol. Cell, 2007;26: 731-743
Google Scholar - 77. Ricci-Vitiani L., Fabrizi E., Palio E., De Maria R.: Colon cancerstem cells. J. Mol. Med., 2009; 87: 1097-1104
Google Scholar - 78. Ricci-Vitiani L., Lombardi D.G., Pilozzi E., Biffoni M., Todaro M.,Peschle C., De Maria R.: Identification and expansion of human colon-cancer-initiating cells. Nature, 2007; 445: 111-115
Google Scholar - 79. Ricci-Vitiani L., Pallini R., Biffoni M., Todaro M., Invernici G.,Cenci T., Maira G., Parati E.A., Stassi G., Larocca L.M., De Maria R.:Tumour vascularization via endothelial differentiation of glioblastomastem-like cells. Nature, 2010; 468: 824-828
Google Scholar - 80. Rogler G.: Chronic ulcerative colitis and colorectal cancer. CancerLett., 2014; 345: 235-241
Google Scholar - 81. Rothenberg M.E., Nusse Y., Kalisky T., Lee J.J., Dalerba P., ScheerenF., Lobo N., Kulkarni S., Sim S., Qian D., Beachy P.A., PasrichaP.J., Quake S.R., Clarke M.F.: Identification of a cKit(+) colonic cryptbase secretory cell that supports Lgr5(+) stem cells in mice. Gastroenterology,2012; 142: 1195-1205
Google Scholar - 82. Roy S., Majumdar A.P.: Cancer stem cells in colorectal cancer:genetic and epigenetic changes. J. Stem Cell Res. Ther., 2012; Suppl. 7
Google Scholar - 83. Salama P., Platell C.: Colorectal cancer stem cells. ANZ J. Surg.,2009; 79: 697-702
Google Scholar - 84. Sangiorgi E., Capecchi M.R.: Bmi1 is expressed in vivo in intestinalstem cells. Nat. Genet., 2008; 40: 915-920
Google Scholar - 85. Sasaki J., Konishi F., Kawamura Y.J., Kai T., Takata O., TsukamotoT.: Clinicopathological characteristics of colorectal cancerswith loss of imprinting of insulin-like growth factor 2. Int. J. Cancer,2006; 119: 80-83
Google Scholar - 86. Sato T., Vries R.G., Snippert H.J., van de Wetering M., BarkerN., Stange D.E., van Es J.H., Abo A., Kujala P., Peters P.J., Clevers H.:Single Lgr5 stem cells build crypt-villus structures in vitro withouta mesenchymal niche. Nature, 2009; 459: 262-265
Google Scholar - 87. Schneider M.R., Hoeflich A., Fischer J.R., Wolf E., Sordat B.,Lahm H.: Interleukin-6 stimulates clonogenic growth of primaryand metastatic human colon carcinoma cells. Cancer Lett., 2000;151: 31-38
Google Scholar - 88. Schwitalla S., Fingerle A.A., Cammareri P., Nebelsiek T., GoktunaS.I., Ziegler P.K., Canli O., Heijmans J., Huels D.J., Moreaux G., RupecR.A., Gerhard M., Schmid R., Barker N., Clevers H. i wsp.: Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem–cell-like properties. Cell, 2013; 152: 25-38
Google Scholar - 89. Sell S.: On the stem cell origin of cancer. Am. J. Pathol., 2010;176: 2584-2594
Google Scholar - 90. Shaker A., Rubin D.C.: Intestinal stem cells and epithelial-mesenchymalinteractions in the crypt and stem cell niche. Transl.Res., 2010; 156: 180-187
Google Scholar - 91. Shih I.M., Wang T.L., Traverso G., Romans K., Hamilton S.R., Ben–Sasson S., Kinzler K.W., Vogelstein B.: Top-down morphogenesis ofcolorectal tumors. Proc. Natl. Acad. Sci. USA, 2001; 98: 2640-2645
Google Scholar - 92. Shmelkov S.V., Butler J.M., Hooper A.T., Hormigo A., KushnerJ., Milde T., St Clair R., Baljevic M., White I., Jin D.K., Chadburn A.,Murphy A.J., Valenzuela D.M., Gale N.W., Thurston G. i wsp.: CD133expression is not restricted to stem cells, and both CD133+ andCD133- metastatic colon cancer cells initiate tumors. J. Clin. Invest.,2008; 118: 2111-2120
Google Scholar - 93. Sikandar S.S., Pate K.T., Anderson S., Dizon D., Edwards R.A.,Waterman M.L., Lipkin S.M.: NOTCH signaling is required for formationand self-renewal of tumor-initiating cells and for repressionof secretory cell differentiation in colon cancer. Cancer Res., 2010;70: 1469-1478
Google Scholar - 94. Snippert H.J., Schepers A.G., van Es J.H., Simons B.D., CleversH.: Biased competition between Lgr5 intestinal stem cells drivenby oncogenic mutation induces clonal expansion. EMBO Rep., 2014;15: 62-69
Google Scholar - 95. Solanas G., Batlle E.: Control of cell adhesion and compartmentalizationin the intestinal epithelium. Exp. Cell Res., 2011; 317:2695-2701
Google Scholar - 96. Stagg J.: Mesenchymal stem cells in cancer. Stem Cell Rev., 2008;4: 119-124
Google Scholar - 97. Steinhauser M.L., Bailey A.P., Senyo S.E., Guillermier C., PerlsteinT.S., Gould A.P., Lee R.T., Lechene C.P.: Multi-isotope imagingmass spectrometry quantifies stem cell division and metabolism.Nature, 2012; 481: 516-519
Google Scholar - 98. Takebe N., Ivy S.P.: Controversies in cancer stem cells: targetingembryonic signaling pathways. Clin. Cancer Res., 2010; 16: 3106-3112
Google Scholar - 99. Tamagawa H., Oshima T., Shiozawa M., Morinaga S., NakamuraY., Yoshihara M., Sakuma Y., Kameda Y., Akaike M., Masuda M., ImadaT., Miyagi Y.: The global histone modification pattern correlateswith overall survival in metachronous liver metastasis of colorectalcancer. Oncol. Rep., 2012; 27: 637-642
Google Scholar - 100. Tan S., Barker N.: Epithelial stem cells and intestinal cancer.Semin. Cancer Biol., 2015; 32: 40-53
Google Scholar - 101. Tchirkov A., Khalil T., Chautard E., Mokhtari K., Véronese L.,Irthum B., Vago P., Kémény J.L., Verrelle P.: Interleukin-6 gene amplificationand shortened survival in glioblastoma patients. Br. J.Cancer, 2007; 96: 474-476
Google Scholar - 102. Tian H., Biehs B., Warming S., Leong K.G., Rangell L., Klein O.D.,de Sauvage F.J.: A reserve stem cell population in small intestinerenders Lgr5-positive cells dispensable. Nature, 2011; 478: 255-259
Google Scholar - 103. Todaro M., Alea M.P., Di Stefano A.B., Cammareri P., VermeulenL., Iovino F., Tripodo C., Russo A., Gulotta G., Medema J.P., Stassi G.:Colon cancer stem cells dictate tumor growth and resist cell deathby production of interleukin-4. Cell Stem Cell., 2007; 1: 389-402
Google Scholar - 104. Todaro M., Perez Alea M., Scopelliti A., Medema J.P., Stassi G.:IL-4-mediated drug resistance in colon cancer stem cells. Cell Cycle,2008; 7: 309-313
Google Scholar - 105. Toyota M., Ahuja N., Ohe-Toyota M., Herman J.G., Baylin S.B.,Issa J.P.: CpG island methylator phenotype in colorectal cancer. Proc.Natl. Acad. Sci. USA, 1999; 96: 8681-8686
Google Scholar - 106. Tsai K.S., Yang S.H., Lei Y.P., Tsai C.C., Chen H.W., Hsu C.Y.,Chen L.L., Wang H.W., Miller S.A., Chiou S.H., Hung M.C., Hung S.C.:Mesenchymal stem cells promote formation of colorectal tumors inmice. Gastroenterology, 2011; 141: 1046-1056
Google Scholar - 107. Uchida H., Yamazaki K., Fukuma M., Yamada T., Hayashida T.,Hasegawa H., Kitajima M., Kitagawa Y., Sakamoto M.: Overexpressionof leucine-rich repeat-containing G protein-coupled receptor 5 incolorectal cancer. Cancer Sci., 2010; 101: 1731-1737
Google Scholar - 108. Umetani N., Takeuchi H., Fujimoto A., Shinozaki M., Bilchik A.J.,Hoon D.S.: Epigenetic inactivation of ID4 in colorectal carcinomascorrelates with poor differentiation and unfavorable prognosis. Clin.Cancer Res., 2004; 10: 7475-7483
Google Scholar - 109. Upadhyay G., Yin Y., Yuan H., Li X., Derynck R., Glazer R.I.: Stemcell antigen-1 enhances tumorigenicity by disruption of growth differentiationfactor-10 (GDF10)-dependent TGF-β signaling. Proc.Natl. Acad. Sci. USA, 2011; 108: 7820-7825
Google Scholar - 110. Vaiopoulos A.G., Kostakis I.D., Koutsilieris M., PapavassiliouA.G.: Colorectal cancer stem cells. Stem Cells, 2012; 30: 363-371
Google Scholar - 111. van der Flier L.G., Haegebarth A., Stange D.E., van de WeteringM., Clevers H.: OLFM4 is a robust marker for stem cells in humanintestine and marks a subset of colorectal cancer cells. Gastroenterology,2009; 137: 15-17
Google Scholar - 112. van der Flier L.G., van Gijn M.E., Hatzis P., Kujala P., HaegebarthA., Stange D.E., Begthel H., van den Born M., Guryev V., OvingI., van Es J.H., Barker N., Peters P.J., van de Wetering M., Clevers H.:Transcription factor achaete scute-like 2 controls intestinal stemcell fate. Cell, 2009; 136: 903-912
Google Scholar - 113. van Es J.H., Sato T., van de Wetering M., Lyubimova A., NeeA.N., Gregorieff A., Sasaki N., Zeinstra L., van den Born M., KorvingJ., Martens A.C., Barker N., van Oudenaarden A., Clevers H.: Dll1+secretory progenitor cells revert to stem cells upon crypt damage.Nat. Cell Biol., 2012; 14: 1099-1104
Google Scholar - 114. Vermeulen L., De Sousa E.M., van der Heijden M., Cameron K., de Jong J.H., Borovski T., Tuynman J.B., Todaro M., Merz C., RodermondH., Sprick M.R., Kemper K., Richel D.J., Stassi G., Medema J.P.:Wnt activity defines colon cancer stem cells and is regulated by themicroenvironment. Nat. Cell Biol., 2010; 12: 468-476
Google Scholar - 115. Vermeulen L., Todaro M., de Sousa Mello F., Sprick M.R., KemperK., Perez Alea M., Richel D.J., Stassi G., Medema J.P.: Single-cellcloning of colon cancer stem cells reveals a multi-lineage differentiationcapacity. Proc. Natl. Acad. Sci. USA, 2008; 105: 13427-13432
Google Scholar - 116. Wong V.W., Stange D.E., Page M.E., Buczacki S., Wabik A., ItamiS., van de Wetering M., Poulsom R., Wright N.A., Trotter M.W., WattF.M., Winton D.J., Clevers H., Jensen K.B.: Lrig1 controls intestinalstem-cell homeostasis by negative regulation of ErbB signalling. Nat.Cell Biol., 2012; 14: 401-408
Google Scholar - 117. Yu J., Tao Q., Cheung K.F., Jin H., Poon F.F., Wang X., Li H., ChengY.Y., Röcken C., Ebert M.P., Chan A.T., Sung J.J.: Epigenetic identificationof ubiquitin carboxyl-terminal hydrolase L1 as a functionaltumor suppressor and biomarker for hepatocellular carcinoma andother digestive tumors. Hepatology, 2008; 48: 508-518
Google Scholar - 118. Zhu L., Gibson P., Currle D.S., Tong Y., Richardson R.J., BayazitovI.T., Poppleton H., Zakharenko S., Ellison D.W., Gilbertson R.J.: Prominin 1 marks intestinal stem cells that are susceptible to neoplastictransformation. Nature, 2009; 457: 603-607
Google Scholar - 119. Zhu S., Si M.L., Wu H., Mo Y.Y.: MicroRNA-21 targets the tumorsuppressor gene tropomyosin 1 (TPM1). J. Biol. Chem., 2007;282: 14328-14336
Google Scholar - 120. Zuo X., Morris J.S., Shureiqi I.: Chromatin modification requirementsfor 15-lipoxygenase-1 transcriptional reactivation in coloncancer cells. J. Biol. Chem., 2008; 283: 31341-31347
Google Scholar