Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Gastroenterology
Published in: Journal of Gastroenterology 10/2011

01-10-2011 | Review

Cancer stem cell theory in gastrointestinal malignancies: recent progress and upcoming challenges

Authors: Dyah Laksmi Dewi, Hideshi Ishii, Yoshihiro Kano, Shinpei Nishikawa, Naotsugu Haraguchi, Daisuke Sakai, Taroh Satoh, Yuichiro Doki, Masaki Mori

Published in: Journal of Gastroenterology | Issue 10/2011

Login to get access

Abstract

A growing body of evidence supports the notion that malignant tumors are heterogeneous and contain diverse subpopulations of cells with unique characteristics including the ability to initiate a tumor and metastasize. This phenomenon might be explained by the so-called cancer stem cell (CSC) theory. Recent technological developments have allowed a deeper understanding and characterization of CSCs. Even though the application of this theory to hematopoietic malignancies and solid tumors holds promise for new ways to treat cancer, it also brings some skepticism. Efficacious therapeutic approaches targeting the CSC population should be explored to overcome therapeutic failure and improve patient outcomes. This review will focus on the intrinsic and extrinsic regulation of CSCs, as well as the development of therapeutic approaches against CSCs, predominantly focusing on gastrointestinal malignancies.
Literature
1.
Dexter DL, Leith JT. Tumor heterogeneity and drug resistance. J Clin Oncol. 1986;4:244–57.PubMed
2.
Adams JM, Strasser A. Is tumor growth sustained by rare cancer stem cells or dominant clones? Cancer Res. 2008;68:4018–21.PubMedCrossRef
3.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.PubMedCrossRef
4.
Shackleton M, Quintana E, Fearon ER, Morrison SJ. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell. 2009;138:822–9.PubMedCrossRef
5.
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.PubMedCrossRef
6.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8.PubMedCrossRef
7.
8.
Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458:780–3.PubMedCrossRef
9.
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;6:603–15.PubMedCrossRef
10.
Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001;7:1028–34.PubMedCrossRef
11.
Goodell MA, Rosenzweig M, Kim H, Marks DF, DeMaria M, Paradis G, et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med. 1997;3:1337–45.PubMedCrossRef
12.
Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 2006;44:240–51.PubMedCrossRef
13.
Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells. 2006;24:506–13.PubMedCrossRef
14.
Ehata S, Johansson E, Katayama R, Koike S, Watanabe A, Hoshino Y, et al. Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells. Oncogene. 2011;30:1693–705.
15.
Smit JW, Schinkel AH, Weert B, Meijer DK. Hepatobiliary and intestinal clearance of amphiphilic cationic drugs in mice in which both mdr1a and mdr1b genes have been disrupted. Br J Pharmacol. 1998;124:416–24.PubMedCrossRef
16.
Mayer U, Wagenaar E, Beijnen JH, Smit JW, Meijer DK, van Asperen J, et al. Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr 1a P-glycoprotein. Br J Pharmacol. 1996;119:1038–44.PubMed
17.
Golebiewska A, Brons NH, Bjerkvig R, Niclou SP. Critical appraisal of the side population assay in stem cell and cancer stem cell research. Cell Stem Cell. 2011;8:136–47.PubMedCrossRef
18.
Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT. CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci. 2004;117:3539–45.PubMedCrossRef
19.
Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997;90:5002–12.PubMed
20.
Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, et al. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA. 2000;97:14720–5.PubMedCrossRef
21.
O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumor growth in immunodeficient mice. Nature. 2007;445:106–10.PubMedCrossRef
22.
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;445:111–5.PubMedCrossRef
23.
Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene. 2008;27:1749–58.PubMedCrossRef
24.
Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133− metastatic colon cancer cells initiate tumors. J Clin Invest. 2008;118:2111–20.PubMed
25.
Huang D, Gao Q, Guo L, Zhang C, Jiang W, Li H, et al. Isolation and identification of cancer stem-like cells in esophageal carcinoma cell lines. Stem Cells Dev. 2009;18:465–73.PubMedCrossRef
26.
Rahadiani N, Ikeda J, Makino T, Tian T, Qiu Y, Mamat S, et al. Tumorigenic role of podoplanin in esophageal squamous-cell carcinoma. Ann Surg Oncol. 2010;17:1311–23.PubMedCrossRef
27.
Zhang X, Komaki R, Wang L, Fang B, Chang JY. Treatment of radioresistant stem-like esophageal cancer cells by an apoptotic gene-armed, telomerase-specific oncolytic adenovirus. Clin Cancer Res. 2008;14:2813–23.PubMedCrossRef
28.
Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009;27:1006–20.PubMedCrossRef
29.
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;1:389–402.PubMedCrossRef
30.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumor initiating cells. Nature. 2004;432:396–401.PubMedCrossRef
31.
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 USA. 2007;104:e10158–63.CrossRef
32.
Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008;13:153–66.PubMedCrossRef
33.
Yang ZF, Ngai P, Ho DW, Yu WC, Ng MN, Lau CK, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. 2008;47:919–28.PubMedCrossRef
34.
Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, et al. Epcam-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009;136:1012–4.PubMedCrossRef
35.
Ma S, Chan KW, Lee TK, Tang KH, Wo JY, Zheng BJ, et al. Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res. 2008;6:1146–53.PubMedCrossRef
36.
Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132:2542–56.PubMedCrossRef
37.
Haraguchi N, Ishii H, Mimori K, Tanaka F, Ohkuma M, Kim HM, et al. CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest. 2010;120:3326–39.PubMedCrossRef
38.
Rege TA, Hagood JS. Thy-1 as a regulator of cell–cell and cell matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB J. 2006;20:1045–54.PubMedCrossRef
39.
Dan YY, Riehle KJ, Lazaro C, Teoh N, Haque J, Campbell JS, et al. Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages. Proc Natl Acad Sci USA. 2006;103:9912–7.PubMedCrossRef
40.
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.PubMedCrossRef
41.
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;1:313–23.PubMedCrossRef
42.
Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006;66:9339–44.PubMedCrossRef
43.
Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumor formation by single human melanoma cells. Nature. 2008;456:593–8.PubMedCrossRef
44.
Vermeulen L, De Sousa E, Melo F, 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;12:468–76.PubMedCrossRef
45.
Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755–68.PubMedCrossRef
46.
47.
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;45:608–11.CrossRef
48.
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;457:603–7.PubMedCrossRef
49.
Bell DR, Van Zant G. Stem cells, aging, and cancer: inevitabilities and outcomes. Oncogene. 2004;23:7290–6.PubMedCrossRef
50.
Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006;442:818–22.PubMedCrossRef
51.
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedCrossRef
52.
Wong DJ, Liu H, Ridky TW, Cassarino D, Segal E, Chang HY. Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell. 2008;2:333–44.PubMedCrossRef
53.
Liu Y, Clem B, Zuba-Surma EK, El-Naggar S, Telang S, Jenson AB, et al. Mouse fibroblasts lacking RB1 function form spheres and undergo reprogramming to a cancer stem cell phenotype. Cell Stem Cell. 2009;4:336–47.PubMedCrossRef
54.
Takebe N, Harris PJ, Warren RQ, Ivy SP. Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol. 2011;8:97–106.PubMedCrossRef
55.
Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008;40:499–507.PubMedCrossRef
56.
Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284:770–6.PubMedCrossRef
57.
Fre S, Pallavi SK, Huyghe M, Laé M, Janssen KP, Robine S, et al. Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine. Proc Natl Acad Sci USA. 2009;106:6309–14.PubMedCrossRef
58.
Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991;66:649–61.PubMedCrossRef
59.
Kopan R, Ilagan MX. The canonical notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137:216–33.PubMedCrossRef
60.
Fre S, Huyghe M, Mourikis P, Robine S, Louvard D, Artavanis-Tsakonas S. Notch signals control the fate of immature progenitor cells in the intestine. Nature. 2005;435:964–8.PubMedCrossRef
61.
Apelqvist A, Ahlgren U, Edlund H. Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas. Curr Biol. 1997;7:801–4.PubMedCrossRef
62.
Kodama Y, Hijikata M, Kageyama R, Shimotohno K, Chiba T. The role of notch signaling in the development of intrahepatic bile ducts. Gastroenterology. 2004;127:1775–86.PubMedCrossRef
63.
Mazur PK, Einwächter H, Lee M, Sipos B, Nakhai H, Rad R, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci USA. 2010;107:13438–43.PubMedCrossRef
64.
Sonoshita M, Aoki M, Fuwa H, Aoki K, Hosogi H, Sakai Y, et al. Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling. Cancer Cell. 2011;19:125–37.PubMedCrossRef
65.
Ohashi S, Natsuizaka M, Yashiro-Ohtani Y, Kalman RA, Nakagawa M, Wu L, et al. NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL-dependent transcriptional network. Gastroenterology. 2010;139:2113–23.PubMedCrossRef
66.
Sikandar SS, Pate KT, Anderson S, Dizon D, Edwards RA, Waterman ML, et al. NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res. 2010;70:1469–78.PubMedCrossRef
67.
68.
van de Wetering M, Molenaar M, Oost-erwegel M, Peterson-Maduro J, Godsave S, Korinek V, et al. The b-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002;111:241–50.PubMedCrossRef
69.
Abu-Remaileh M, Gerson A, Farago M, Nathan G, Alkalay I, Zins Rousso S, et al. Oct-3/4 regulates stem cell identity and cell fate decisions by modulating Wnt/β-catenin signaling. EMBO J. 2010;29:3236–48.PubMedCrossRef
70.
Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumors. Nature. 2003;425:846–51.PubMedCrossRef
71.
Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P, et al. Human colon cancer epithelial cells harbor active HEDGEHOG-GLI signaling that is essential for tumor growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med. 2009;1:338–51.PubMedCrossRef
72.
Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003;425:851–6.PubMedCrossRef
73.
Watabe T, Miyazono K. Roles of TGF-beta family signaling in stem cell renewal and differentiation. Cell Res. 2009;19:103–15.PubMedCrossRef
74.
Ikushima H, Miyazono K. TGFβ signalling: a complex web in cancer progression. Nat Rev Cancer. 2010;10:415–24.PubMedCrossRef
75.
Takaku M, Oshima M, Miyoshi H, Matsui M, Seldin MF, Taketo MM. Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes. Cell. 1998;92:645–56.PubMedCrossRef
76.
Kabashima A, Higuchi H, Takaishi H, Matsuzaki Y, Suzuki S, Izumiya M, et al. Side population of pancreatic cancer cells predominates in TGF-beta-mediated epithelial to mesenchymal transition and invasion. Int J Cancer. 2009;124:2771–9.PubMedCrossRef
77.
Tang B, Yoo N, Vu M, Mamura M, Nam JS, Ooshima A, et al. Transforming growth factor β can suppress tumorigenesis through effects on the putative cancer stem or early progenitor cell and committed progeny in a breast cancer xenograft model. Cancer Res. 2007;67:8643–52.PubMedCrossRef
78.
79.
Berdasco M, Esteller M. Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell. 2010;19:698–711.PubMedCrossRef
80.
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.PubMedCrossRef
81.
82.
Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006;125:315–26.PubMedCrossRef
83.
Nguyen CT, Weisenberger DJ, Velicescu M, Gonzales FA, Lin JC, Liang G, et al. Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2’-deoxycytidine. Cancer Res. 2002;62:6456–61.PubMed
84.
Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005;37:391–400.PubMedCrossRef
85.
Yasuda H, Soejima K, Watanabe H, Kawada I, Nakachi I, Yoda S, et al. Distinct epigenetic regulation of tumor suppressor genes in putative cancer stem cells of solid tumors. Int J Oncol. 2010;37:1537–46.PubMed
86.
Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, et al. Global histone modification patterns predict risk of prostate cancer recurrence. Nature. 2005;435:1262–6.PubMedCrossRef
87.
You H, Ding W, Rountree CB. Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-beta. Hepatology. 2010;51:1635–44.PubMedCrossRef
88.
Hernandez-Vargas H, Ouzounova M, Calvez-Kelm FL, Lambert MP, McKay-Chopin S, Tavtigian SV, et al. Methylome analysis reveals Jak-STAT pathway deregulation in putative breast cancer stem cells. Epigenetics. 2011;6:428–39.
89.
90.
O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435:839–43.PubMedCrossRef
91.
Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell. 2005;120:635–47.PubMedCrossRef
92.
Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, et al. Dicer is essential for mouse development. Nat Genet. 2003;35:215–7.PubMedCrossRef
93.
Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, et al. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 2005;19:489–501.PubMedCrossRef
94.
McKenna LB, Schug J, Vourekas A, McKenna JB, Bramswig NC, Friedman JR, et al. MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function. Gastroenterology. 2010;139:1654–64.PubMedCrossRef
95.
Sekine S, Ogawa R, Ito R, Hiraoka N, McManus MT, Kanai Y, et al. Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis. Gastroenterology. 2009;136:2304–15.PubMedCrossRef
96.
Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, et al. Human embryonic stem cells express a unique set of microRNAs. Dev Biol. 2004;270:488–98.PubMedCrossRef
97.
Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39:673–7.PubMedCrossRef
98.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.PubMedCrossRef
99.
Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology. 2009;502:472–80.CrossRef
100.
Wang Y, Yu Y, Tsuyada A, Ren X, Wu X, Stubblefield K, et al. Transforming growth factor-b regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and ATM. Oncogene. 2011;30:1470–80.
101.
Wang B, Hsu SH, Majumder S, Kutay H, Huang W, Jacob ST, et al. TGF beta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene. 2010;29:1787–97.PubMedCrossRef
102.
Ma S, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, et al. miR-130b Promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell. 2010;7:694–707.PubMedCrossRef
103.
Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011;17:211–5.PubMedCrossRef
104.
Iliopoulos D, Lindahl-Allen M, Polytarchou C, Hirsch HA, Tsichlis PN, Struhl K. Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol Cell. 2010;39:761–72.PubMedCrossRef
105.
Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature. 2004;432:332–7.PubMedCrossRef
106.
Morrison SJ, Spradling AC. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 2008;132:598–611.PubMedCrossRef
107.
108.
Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, et al. Variable β-catenin expression in colorectal cancer indicates tumor progression driven by tumor environment. Proc Natl Acad Sci USA. 2001;98:10356–61.PubMedCrossRef
109.
Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11:69–82.PubMedCrossRef
110.
Iliopoulos D, Hirsch HA, Wang G, Struhl K. Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci USA. 2011;108:1397–402.PubMedCrossRef
111.
Mazumdar J, O’Brien WT, Johnson RS, LaManna JC, Chavez JC, Klein PS, et al. O2 regulates stem cells through Wnt/β-catenin signaling. Nat Cell Biol. 2010;12:1007–13.PubMedCrossRef
112.
Yeung TM, Gandhi SC, Bodmer WF. Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells. Proc Natl Acad Sci USA. 2011;108:4382–7.
113.
Soeda A, Park M, Lee D, Mintz A, Androutsellis-Theotokis A, McKay RD, et al. Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene. 2009;28:3949–59.PubMedCrossRef
114.
Heddleston JM, Li Z, McLendon RE, Hjelmeland AB, Rich JN. The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle. 2009;8:3274–84.PubMedCrossRef
115.
Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138:645–59.PubMedCrossRef
116.
Dong TT, Zhou HM, Wang LL, Feng B, Lv B, Zheng MH. Salinomycin selectively targets ‘CD133+’ cell subpopulations and decreases malignant traits in colorectal cancer lines. Ann Surg Oncol. 2011;18:1797–804.
117.
Mueller MT, Hermann PC, Witthauer J, Rubio-Viqueira B, Leicht SF, Huber S, et al. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology. 2009;137:1102–13.PubMedCrossRef
118.
Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12:1167–74.PubMedCrossRef
119.
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;69:3382–9.PubMedCrossRef
120.
Zhu Z, Hao X, Yan M, Yao M, Ge C, Gu J, et al. Cancer stem/progenitor cells are highly enriched in CD133+ CD44+ population in hepatocellular carcinoma. Int J Cancer. 2010;126:2067–78.PubMedCrossRef
121.
Hwang-Verslues WW, Chang PH, Wei PC, Yang CY, Huang CK, Kuo WH, et al. miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1. Oncogene. 2011;30:2463–74.
122.
Henry JC, Park JK, Jiang J, Kim JH, Nagorney DM, Roberts LR, et al. miR-199a–3p targets CD44 and reduces proliferation of CD44 positive hepatocellular carcinoma cell lines. Biochem Biophys Res Commun. 2010;403:120–5.PubMedCrossRef
123.
Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131:1109–23.PubMedCrossRef
124.
Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138:592–603.PubMedCrossRef
125.
Yu F, Deng H, Yao H, Liu Q, Su F, Song E. Mir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells. Oncogene. 2010;29:4194–204.PubMedCrossRef
Metadata
Title
Cancer stem cell theory in gastrointestinal malignancies: recent progress and upcoming challenges
Authors
Dyah Laksmi Dewi
Hideshi Ishii
Yoshihiro Kano
Shinpei Nishikawa
Naotsugu Haraguchi
Daisuke Sakai
Taroh Satoh
Yuichiro Doki
Masaki Mori
Publication date
01-10-2011
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 10/2011
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-011-0442-6

Other articles of this Issue 10/2011

Journal of Gastroenterology 10/2011 Go to the issue

Original Article—Alimentary Tract

Daikenchuto (TU-100) ameliorates colon microvascular dysfunction via endogenous adrenomedullin in Crohn’s disease rat model

Original Article—Liver, Pancreas, and Biliary Tract

A large volume of visceral adipose tissue leads to severe acute pancreatitis

Original Article—Liver, Pancreas, and Biliary Tract

Phenotype-dependent production of des-γ-carboxy prothrombin in hepatocellular carcinoma

Original Article—Alimentary Tract

Expression of angiotensin II type 1 and type 2 receptor mRNAs in the gastric mucosa of Helicobacter pylori-infected Mongolian gerbils

Original Article—Liver, Pancreas, and Biliary Tract

Evaluation of liver fibrosis by transient elastography using acoustic radiation force impulse: comparison with Fibroscan®

Original Article—Alimentary Tract

Gastric acid induces mitochondrial superoxide production and lipid peroxidation in gastric epithelial cells
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits