Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177–93.
Article
PubMed
Google Scholar
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.
Article
CAS
PubMed
Google Scholar
Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61(5):759–67.
Article
CAS
PubMed
Google Scholar
de Sousa e Melo F, Kurtova AV, Harnoss JM, Kljavin N, Hoeck JD, Hung J, et al. A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer. Nature. 2017;543(7647):676–680.
Lenos KJ, Miedema DM, Lodestijn SC, Nijman LE, van den Bosch T, Romero Ros X, et al. Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer. Nat Cell Biol. 2018;20(10):1193–202.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 2010;12(5):468–476.
De Sousa EMF, Vermeulen L, Fessler E, Medema JP. Cancer heterogeneity--a multifaceted view. EMBO Rep 2013;14(8):686–695.
Linnekamp JF, Wang X, Medema JP, Vermeulen L. Colorectal cancer heterogeneity and targeted therapy: a case for molecular disease subtypes. Cancer Res. 2015;75(2):245–9.
Article
CAS
PubMed
Google Scholar
De Sousa EMF, Wang X, Jansen M, Fessler E, Trinh A, de Rooij LP, et al. Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 2013;19(5):614–618.
Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6.
Article
CAS
PubMed
PubMed Central
Google Scholar
Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457(7229):608–11.
Article
CAS
PubMed
Google Scholar
Bjerknes M, Cheng H. Clonal analysis of mouse intestinal epithelial progenitors. Gastroenterology. 1999;116(1):7–14.
Article
CAS
PubMed
Google Scholar
Clevers H. The intestinal crypt, a prototype stem cell compartment. Cell. 2013;154(2):274–84.
Article
CAS
PubMed
Google Scholar
Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449(7165):1003–7.
Article
CAS
PubMed
Google Scholar
Cheng H, Leblond CP. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. I Columnar cell Am J Anat 1974;141(4):461–479.
Cheng H, Leblond CP. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian theory of the origin of the four epithelial cell types. Am J Anat. 1974;141(4):537–61.
Article
CAS
PubMed
Google Scholar
Sangiorgi E, Capecchi MR. Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. 2008;40(7):915–20.
Article
CAS
PubMed
PubMed Central
Google Scholar
Takeda N, Jain R, LeBoeuf MR, Wang Q, Lu MM, Epstein JA. Interconversion between intestinal stem cell populations in distinct niches. Science. 2011;334(6061):1420–1424.
Munoz J, Stange DE, Schepers AG, van de Wetering M, Koo BK, Itzkovitz S, et al. The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4′ cell markers. EMBO J. 2012;31(14):3079–91.
Article
CAS
PubMed
PubMed Central
Google Scholar
Montgomery RK, Carlone DL, Richmond CA, Farilla L, Kranendonk ME, Henderson DE, et al. Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc Natl Acad Sci U S A 2011;108(1):179–184.
van der Flier LG, van Gijn ME, Hatzis P, Kujala P, Haegebarth A, Stange DE, et al. Transcription factor achaete scute-like 2 controls intestinal stem cell fate. Cell. 2009;136(5):903–12.
Article
PubMed
CAS
Google Scholar
Powell AE, Wang Y, Li Y, Poulin EJ, Means AL, Washington MK, et al. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell. 2012;149(1):146–58.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, et al. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature. 2009;457(7229):603–7.
Article
CAS
PubMed
Google Scholar
Snippert HJ, van Es JH, van den Born M, Begthel H, Stange DE, Barker N, et al. Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine. Gastroenterology. 2009;136(7):2187–2194 e1.
Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469(7330):415–8.
Article
CAS
PubMed
Google Scholar
Baker AM, Cereser B, Melton S, Fletcher AG, Rodriguez-Justo M, Tadrous PJ, et al. Quantification of crypt and stem cell evolution in the normal and neoplastic human colon. Cell Rep. 2014;8(4):940–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lopez-Garcia C, Klein AM, Simons BD, Winton DJ. Intestinal stem cell replacement follows a pattern of neutral drift. Science. 2010;330(6005):822–5.
Article
CAS
PubMed
Google Scholar
Snippert HJ, van der Flier LG, Sato T, van Es JH, van den Born M, Kroon-Veenboer C, et al. Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell. 2010;143(1):134–44.
Article
CAS
PubMed
Google Scholar
Ritsma L, Ellenbroek SIJ, Zomer A, Snippert HJ, de Sauvage FJ, Simons BD, et al. Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature. 2014;507(7492):362–5.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kozar S, Morrissey E, Nicholson AM, van der Heijden M, Zecchini HI, Kemp R, et al. Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas. Cell Stem Cell. 2013;13(5):626–33.
Article
CAS
PubMed
Google Scholar
Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011;478(7368):255–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Metcalfe C, Kljavin NM, Ybarra R, de Sauvage FJ. Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell. 2014;14(2):149–59.
Article
CAS
PubMed
Google Scholar
Tetteh PW, Basak O, Farin HF, Wiebrands K, Kretzschmar K, Begthel H, et al. Replacement of lost Lgr5-positive stem cells through plasticity of their enterocyte-lineage daughters. Cell Stem Cell. 2016;18(2):203–13.
Article
CAS
PubMed
Google Scholar
van Es JH, Sato T, van de Wetering M, Lyubimova A, Nee AN, Gregorieff A, et al. Dll1+ secretory progenitor cells revert to stem cells upon crypt damage. Nat Cell Biol 2012;14(10):1099–1104.
Tomic G, Morrissey E, Kozar S, Ben-Moshe S, Hoyle A, Azzarelli R, et al. Phospho-regulation of ATOH1 is required for plasticity of secretory progenitors and tissue regeneration. Cell Stem Cell. 2018.
Asfaha S, Hayakawa Y, Muley A, Stokes S, Graham TA, Ericksen RE, et al. Krt19(+)/Lgr5(−) cells are Radioresistant Cancer-initiating stem cells in the Colon and Intestine. Cell Stem Cell. 2015;16(6):627–38.
Article
CAS
PubMed
PubMed Central
Google Scholar
Barriga FM, Montagni E, Mana M, Mendez-Lago M, Hernando-Momblona X, Sevillano M, et al. Mex3a Marks a slowly dividing subpopulation of Lgr5+ intestinal stem cells. Cell Stem Cell 2017;20(6):801–816 e7.
Vermeulen L, Snippert HJ. Stem cell dynamics in homeostasis and cancer of the intestine. Nat Rev Cancer. 2014;14(7):468–80.
Article
CAS
PubMed
Google Scholar
Buczacki SJ, Zecchini HI, Nicholson AM, Russell R, Vermeulen L, Kemp R, et al. Intestinal label-retaining cells are secretory precursors expressing Lgr5. Nature. 2013;495(7439):65–69.
Jadhav U, Saxena M, O'Neill NK, Saadatpour A, Yuan GC, Herbert Z, et al. Dynamic reorganization of chromatin accessibility signatures during dedifferentiation of secretory precursors into Lgr5+ intestinal stem cells. Cell Stem Cell 2017;21(1):65–77 e5.
Kaaij LT, van de Wetering M, Fang F, Decato B, Molaro A, van de Werken HJ, et al. DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus. Genome Biol 2013;14(5):R50.
Kim TH, Li F, Ferreiro-Neira I, Ho LL, Luyten A, Nalapareddy K, et al. Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity. Nature. 2014;506(7489):511–5.
Article
CAS
PubMed
PubMed Central
Google Scholar
Yan KS, Gevaert O, Zheng GXY, Anchang B, Probert CS, Larkin KA, et al. Intestinal Enteroendocrine lineage cells possess homeostatic and injury-inducible stem cell activity. Cell Stem Cell 2017;21(1):78–90 e6.
Schmitt M, Schewe M, Sacchetti A, Feijtel D, van de Geer WS, Teeuwssen M, et al. Paneth cells respond to inflammation and contribute to tissue regeneration by acquiring stem-like features through SCF/c-kit signaling. Cell Rep 2018;24(9):2312–2328 e7.
Yu S, Tong K, Zhao Y, Balasubramanian I, Yap GS, Ferraris RP, et al. Paneth cell multipotency induced by notch activation following injury. Cell Stem Cell 2018;23(1):46–59 e5.
Voog J, Jones DL. Stem cells and the niche: a dynamic duo. Cell Stem Cell. 2010;6(2):103–15.
Article
CAS
PubMed
PubMed Central
Google Scholar
Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet. 1998;19(4):379–83.
Article
CAS
PubMed
Google Scholar
Farin HF, Van Es JH, Clevers H. Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells. Gastroenterology. 2012;143(6):1518–1529 e7.
Valenta T, Degirmenci B, Moor AE, Herr P, Zimmerli D, Moor MB, et al. Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis. Cell Rep. 2016;15(5):911–8.
Article
CAS
PubMed
Google Scholar
Shoshkes-Carmel M, Wang YJ, Wangensteen KJ, Toth B, Kondo A, Massasa EE, et al. Subepithelial telocytes are an important source of Wnts that supports intestinal crypts. Nature. 2018;557(7704):242–6.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wong VW, Stange DE, Page ME, Buczacki S, Wabik A, Itami S, et al. Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nat Cell Biol 2012;14(4):401–408.
Haramis AP, Begthel H, van den Born M, van Es J, Jonkheer S, Offerhaus GJ, et al. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science. 2004;303(5664):1684–6.
Article
CAS
PubMed
Google Scholar
Kosinski C, Li VS, Chan AS, Zhang J, Ho C, Tsui WY, et al. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci U S A 2007;104(39):15418–15423.
Spit M, Koo BK, Maurice MM. Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and cancer. Open Biol. 2018;8(9).
Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, et al. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet. 2001;28(2):184–7.
Article
CAS
PubMed
Google Scholar
He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, et al. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 2004;36(10):1117–1121.
Pellegrinet L, Rodilla V, Liu Z, Chen S, Koch U, Espinosa L, et al. Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells. Gastroenterology. 2011;140(4):1230–40 e1–7.
van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, Begthel H, et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005;435(7044):959–63.
Article
PubMed
CAS
Google Scholar
Yang Q, Bermingham NA, Finegold MJ, Zoghbi HY. Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science. 2001;294(5549):2155–8.
Article
CAS
PubMed
Google Scholar
Basak O, Beumer J, Wiebrands K, Seno H, van Oudenaarden A, Clevers H. Induced quiescence of Lgr5+ stem cells in intestinal organoids enables differentiation of hormone-producing Enteroendocrine cells. Cell Stem Cell 2017;20(2):177–190 e4.
Beumer J, Artegiani B, Post Y, Reimann F, Gribble F, Nguyen TN, et al. Enteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient. Nat Cell Biol. 2018;20(8):909–16.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rothenberg ME, Nusse Y, Kalisky T, Lee JJ, Dalerba P, Scheeren F, et al. Identification of a cKit(+) colonic crypt base secretory cell that supports Lgr5(+) stem cells in mice. Gastroenterology. 2012;142(5):1195–1205 e6.
Sasaki N, Sachs N, Wiebrands K, Ellenbroek SI, Fumagalli A, Lyubimova A, et al. Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon. Proc Natl Acad Sci U S A 2016;113(37):E5399–E5407.
Degirmenci B, Valenta T, Dimitrieva S, Hausmann G, Basler K. GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells. Nature. 2018;558(7710):449–53.
Article
CAS
PubMed
Google Scholar
Jung P, Sato T, Merlos-Suarez A, Barriga FM, Iglesias M, Rossell D, et al. Isolation and in vitro expansion of human colonic stem cells. Nat Med. 2011;17(10):1225–7.
Article
CAS
PubMed
Google Scholar
Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Nat Med. 2012;18(4):618–23.
Article
CAS
PubMed
Google Scholar
Hirata A, Utikal J, Yamashita S, Aoki H, Watanabe A, Yamamoto T, et al. Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium. Development. 2013;140(1):66–75.
Nicholson AM, Olpe C, Hoyle A, Thorsen AS, Rus T, Colombe M, et al. Fixation and spread of somatic mutations in adult human colonic epithelium. Cell Stem Cell 2018;22(6):909–918 e8.
Visvader JE. Cells of origin in cancer. Nature. 2011;469(7330):314–22.
Article
CAS
PubMed
Google Scholar
Shih IM, Wang TL, Traverso G, Romans K, Hamilton SR, Ben-Sasson S, et al. Top-down morphogenesis of colorectal tumors. Proc Natl Acad Sci U S A. 2001;98(5):2640–5.
Article
CAS
PubMed
PubMed Central
Google Scholar
Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.
Article
CAS
PubMed
Google Scholar
Shibata H, Toyama K, Shioya H, Ito M, Hirota M, Hasegawa S, et al. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science. 1997;278(5335):120–3.
Article
CAS
PubMed
Google Scholar
Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Goktuna SI, Ziegler PK, et al. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell. 2013;152(1–2):25–38.
Article
CAS
PubMed
Google Scholar
van der Heijden M, Zimberlin CD, Nicholson AM, Colak S, Kemp R, Meijer SL, et al. Bcl-2 is a critical mediator of intestinal transformation. Nat Commun. 2016;7:10916.
Article
PubMed
PubMed Central
CAS
Google Scholar
Westphalen CB, Asfaha S, Hayakawa Y, Takemoto Y, Lukin DJ, Nuber AH, et al. Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J Clin Invest. 2014;124(3):1283–95.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nakanishi Y, Seno H, Fukuoka A, Ueo T, Yamaga Y, Maruno T, et al. Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat Genet. 2013;45(1):98–103.
Article
CAS
PubMed
Google Scholar
Jess T, Rungoe C, Peyrin-Biroulet L. Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol 2012;10(6):639–645.
Jansen M, Langeveld D, De Leng WW, Milne AN, Giardiello FM, Offerhaus GJ. LKB1 as the ghostwriter of crypt history. Familial Cancer 2011;10(3):437–446.
Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J, et al. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006;355(9):885–95.
Article
CAS
PubMed
Google Scholar
Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377(9759):31–41.
Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, et al. A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut. 2002;50(6):857–60.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cuzick J, Otto F, Baron JA, Brown PH, Burn J, Greenwald P, et al. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol. 2009;10(5):501–7.
Article
CAS
PubMed
Google Scholar
Vermeulen L, Morrissey E, van der Heijden M, Nicholson AM, Sottoriva A, Buczacki S, et al. Defining stem cell dynamics in models of intestinal tumor initiation. Science. 2013;342(6161):995–8.
Article
CAS
PubMed
Google Scholar
Snippert HJ, Schepers AG, van Es JH, Simons BD, Clevers H. Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induces clonal expansion. EMBO Rep. 2014;15(1):62–9.
Article
CAS
PubMed
Google Scholar
Bruens L, Ellenbroek SIJ, van Rheenen J, Snippert HJ. In vivo imaging reveals existence of crypt fission and fusion in adult mouse intestine. Gastroenterology. 2017;153(3):674–677 e3.
Cairnie AB, Millen BH. Fission of crypts in the small intestine of the irradiated mouse. Cell Tissue Kinet. 1975;8(2):189–96.
CAS
PubMed
Google Scholar
Cheng H, Bjerknes M, Amar J, Gardiner G. Crypt production in normal and diseased human colonic epithelium. Anat Rec. 1986;216(1):44–8.
Article
CAS
PubMed
Google Scholar
Graham TA, Humphries A, Sanders T, Rodriguez-Justo M, Tadrous PJ, Preston SL, et al. Use of methylation patterns to determine expansion of stem cell clones in human colon tissue. Gastroenterology. 2011;140(4):1241–50 e1–9.
Greaves LC, Preston SL, Tadrous PJ, Taylor RW, Barron MJ, Oukrif D, et al. Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission. Proc Natl Acad Sci U S A. 2006;103(3):714–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Leedham SJ, Graham TA, Oukrif D, McDonald SA, Rodriguez-Justo M, Harrison RF, et al. Clonality, founder mutations, and field cancerization in human ulcerative colitis-associated neoplasia. Gastroenterology. 2009;136(2):542–550 e6.
Stryker SJ, Wolff BG, Culp CE, Libbe SD, Ilstrup DM, MacCarty RL. Natural history of untreated colonic polyps. Gastroenterology. 1987;93(5):1009–1013.
Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science. 2012;337(6095):730–5.
Article
CAS
PubMed
Google Scholar
Humphries A, Cereser B, Gay LJ, Miller DS, Das B, Gutteridge A, et al. Lineage tracing reveals multipotent stem cells maintain human adenomas and the pattern of clonal expansion in tumor evolution. Proc Natl Acad Sci U S A 2013;110(27):E2490–E2499.
van den Brink GR, Offerhaus GJ. The morphogenetic code and colon cancer development. Cancer Cell. 2007;11(2):109–17.
Article
PubMed
CAS
Google Scholar
Wong WM, Mandir N, Goodlad RA, Wong BC, Garcia SB, Lam SK, et al. Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission. Gut. 2002;50(2):212–7.
Article
PubMed
PubMed Central
Google Scholar
Vermeulen L, de Sousa e Melo F, Richel DJ, Medema JP. The developing cancer stem-cell model: clinical challenges and opportunities. Lancet Oncol. 2012;13(2):e83–e89.
Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells--old concepts, new insights. Cell Death Differ. 2008;15(6):947–58.
Article
CAS
PubMed
Google Scholar
Vermeulen L, Todaro M, de Sousa Mello F, Sprick MR, Kemper K, Perez Alea M, et al. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci U S A 2008;105(36):13427–13432.
Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F, Biffoni M, et al. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell. 2014;14(3):342–56.
Article
CAS
PubMed
Google Scholar
Shimokawa M, Ohta Y, Nishikori S, Matano M, Takano A, Fujii M, et al. Visualization and targeting of LGR5+ human colon cancer stem cells. Nature. 2017.
Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Cespedes MV, et al. Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation. Cancer Cell 2012;22(5):571–584.
Yusra, Semba S, Yokozaki H. Biological significance of tumor budding at the invasive front of human colorectal carcinoma cells. Int J Oncol 2012;41(1):201–210.
Zubeldia IG, Bleau AM, Redrado M, Serrano D, Agliano A, Gil-Puig C, et al. Epithelial to mesenchymal transition and cancer stem cell phenotypes leading to liver metastasis are abrogated by the novel TGFbeta1-targeting peptides P17 and P144. Exp Cell Res 2013;319(3):12–22.
Lotti F, Jarrar AM, Pai RK, Hitomi M, Lathia J, Mace A, et al. Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A. J Exp Med. 2013;210(13):2851–72.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730–7.
Article
CAS
PubMed
Google Scholar
Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–8.
Article
CAS
PubMed
Google Scholar
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100(7):3983–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396–401.
Article
CAS
PubMed
Google Scholar
Cortina C, Turon G, Stork D, Hernando-Momblona X, Sevillano M, Aguilera M, et al. A genome editing approach to study cancer stem cells in human tumors. EMBO Mol Med. 2017;9(7):869–79.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104(24):10158–63.
Article
CAS
PubMed
PubMed Central
Google Scholar
Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69(8):3382–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem Cells. 2012;30(11):2378–86.
Article
CAS
PubMed
Google Scholar
Merlos-Suarez A, Barriga FM, Jung P, Iglesias M, Cespedes MV, Rossell D, et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. 2011;8(5):511–24.
Article
CAS
PubMed
Google Scholar
O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106–110.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111–5.
Article
CAS
PubMed
Google Scholar
Pang R, Law WL, Chu AC, Poon JT, Lam CS, Chow AK, et al. A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 2010;6(6):603–615.
Grillet F, Bayet E, Villeronce O, Zappia L, Lagerqvist EL, Lunke S, et al. Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture. Gut. 2017;66(10):1802–10.
Orian-Rousseau V. CD44, a therapeutic target for metastasising tumours. Eur J Cancer. 2010;46(7):1271–7.
Article
CAS
PubMed
Google Scholar
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555–67.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1(3):313–23.
Article
CAS
PubMed
Google Scholar
Takaya A, Hirohashi Y, Murai A, Morita R, Saijo H, Yamamoto E, et al. Establishment and analysis of Cancer stem-like and non-Cancer stem-like clone cells from the human Colon Cancer cell line SW480. PLoS One. 2016;11(7):e0158903.
Article
PubMed
PubMed Central
CAS
Google Scholar
Francescangeli F, Contavalli P, De Angelis ML, Baiocchi M, Gambara G, Pagliuca A, et al. Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer. Cell Death Differ. 2015;22(10):1700–13.
Article
CAS
PubMed
PubMed Central
Google Scholar
Blanpain C, Simons BD. Unravelling stem cell dynamics by lineage tracing. Nat Rev Mol Cell Biol. 2013;14(8):489–502.
Article
CAS
PubMed
Google Scholar
Lamprecht S, Schmidt EM, Blaj C, Hermeking H, Jung A, Kirchner T, et al. Multicolor lineage tracing reveals clonal architecture and dynamics in colon cancer. Nat Commun. 2017;8(1):1406.
Article
PubMed
PubMed Central
CAS
Google Scholar
Nguyen LV, Cox CL, Eirew P, Knapp DJ, Pellacani D, Kannan N, et al. DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts. Nat Commun 2014;5:5871.
Kreso A, O'Brien CA, van Galen P, Gan OI, Notta F, Brown AM, et al. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science. 2013;339(6119):543–548.
Dieter SM, Ball CR, Hoffmann CM, Nowrouzi A, Herbst F, Zavidij O, et al. Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. Cell Stem Cell. 2011;9(4):357–65.
Article
CAS
PubMed
Google Scholar
Siegmund KD, Marjoram P, Woo YJ, Tavare S, Shibata D. Inferring clonal expansion and cancer stem cell dynamics from DNA methylation patterns in colorectal cancers. Proc Natl Acad Sci U S A. 2009;106(12):4828–33.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sottoriva A, Spiteri I, Shibata D, Curtis C, Tavare S. Single-molecule genomic data delineate patient-specific tumor profiles and cancer stem cell organization. Cancer Res. 2013;73(1):41–9.
Article
CAS
PubMed
Google Scholar
Pisco AO, Huang S. Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: 'What does not kill me strengthens me'. Br J Cancer. 2015;112(11):1725–32.
Article
CAS
PubMed
PubMed Central
Google Scholar
Colak S, Zimberlin CD, Fessler E, Hogdal L, Prasetyanti PR, Grandela CM, et al. Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells. Cell Death Differ. 2014;21(7):1170–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dylla SJ, Beviglia L, Park IK, Chartier C, Raval J, Ngan L, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One. 2008;3(6):e2428.
Article
PubMed
PubMed Central
CAS
Google Scholar
Lombardo Y, Scopelliti A, Cammareri P, Todaro M, Iovino F, Ricci-Vitiani L, et al. Bone morphogenetic protein 4 induces differentiation of colorectal cancer stem cells and increases their response to chemotherapy in mice. Gastroenterology. 2011;140(1):297–309.
Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007;1(4):389–402.
Article
CAS
PubMed
Google Scholar
Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, et al. Targeting notch, hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol. 2015;12(8):445–64.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gong X, Azhdarinia A, Ghosh SC, Xiong W, An Z, Liu Q, et al. LGR5-targeted antibody-drug conjugate eradicates gastrointestinal tumors and prevents recurrence. Mol Cancer Ther. 2016;15(7):1580–90.
Article
CAS
PubMed
Google Scholar
Junttila MR, Mao W, Wang X, Wang BE, Pham T, Flygare J, et al. Targeting LGR5+ cells with an antibody-drug conjugate for the treatment of colon cancer. Sci Transl Med. 2015;7(314):314ra186.
Storm EE, Durinck S, de Sousa e Melo F, Tremayne J, Kljavin N, tan C, et al. targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature. 2016;529(7584):97–100.
Koo BK, van Es JH, van den Born M, Clevers H. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia. Proc Natl Acad Sci U S A. 2015;112(24):7548–50.
Article
CAS
PubMed
PubMed Central
Google Scholar
Batlle E, Clevers H. Cancer stem cells revisited. Nat Med. 2017;23(10):1124–34.
Article
CAS
PubMed
Google Scholar
Bendell JC, Hochster H, Hart LL, Firdaus I, Mace JR, McFarlane JJ, et al. A phase II randomized trial (GO27827) of first-line FOLFOX plus bevacizumab with or without the MET inhibitor Onartuzumab in patients with metastatic colorectal Cancer. Oncologist. 2017;22(3):264–271.
van der Horst EH, Chinn L, Wang M, Velilla T, Tran H, Madrona Y, et al. Discovery of fully human anti-MET monoclonal antibodies with antitumor activity against colon cancer tumor models in vivo. Neoplasia. 2009;11(4):355–364.
Gupta PB, Fillmore CM, Jiang G, Shapira SD, Tao K, Kuperwasser C, et al. Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell. 2011;146(4):633–44.
Article
CAS
PubMed
Google Scholar
Zeuner A, Todaro M, Stassi G, De Maria R. Colorectal cancer stem cells: from the crypt to the clinic. Cell Stem Cell. 2014;15(6):692–705.
Article
CAS
PubMed
Google Scholar