Basic & Clinical Cancer Research 2018. 10(2):33-48.

Curcumin suppresses colorectal cancer progression through down-regulation of Wnt signaling in cancer stem cells
Reyhaneh Moradi-Marjaneh, Seyed Mahdi Hassanian, Soodabeh Shahidsales, Amir Avan, Majid Khazaei

Abstract


Colorectal cancer (CRC) is a leading cause of death worldwide. Despite improved treatment procedures, the disease rarely can be cured completely mainly because of recurrence. It is well evident that cancer recurrence is caused by cancer stem cells (CSCs), rare and immortal cells that can initiate and develop tumors and protect them against anticancer agents. CSCs are generated as a result of failures in intracellular signaling pathways of which Wnt/β-catenin has a key role in CRC. The Wnt/β-catenin signaling pathway is thought to be the major signaling in the maintenance of homeostasis of intestinal stem cells. Proliferation, upward migration of the colony crypt daughter cells, and differentiation into all epithelial cell types at least in part is regulated by Wnt/β-catenin signaling, suggesting its essential role during intestinal development and homeostasis. However, continuous activation of this signaling pathway in intestinal stem cells due to somatic mutations is a hallmark of most CRCs. Hence targeting Wnt/β-catenin signaling in CSCs can be a focus of new treatment strategies. Curcumin, the effective compound of plant Curcuma longa, has been studied as an anticancer agent. Recently, it has been shown that curcumin and its analogues decrease the risk of tumor recurrence by targeting CSCs via various cell signaling, in particular, Wnt/β-catenin pathway. In this review, we describe a relationship between Wnt-regulated CSCs and progression of CRC and the efficacy of curcumin and its analogues in targeting colorectal CSCs and also the Wnt/β-catenin molecular pathway involved.


Keywords


Wnt/β-catenin pathway, Colorectal cancer, cancer stem cells

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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.

Clevers H. At the crossroads of inflammation and cancer. Cell. 2004;118(6):671-4.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA: a cancer journal for clinicians. 2008;58(2):71-96.

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.

Adams PD, Jasper H, Rudolph KL. Aging-induced stem cell mutations as drivers for disease and cancer. Cell stem cell. 2015;16(6):601-12.

Wielenga VJ, Smits R, Korinek V, Smit L, Kielman M, Fodde R, et al. Expression of CD44 in Apc and TcfMutant Mice Implies Regulation by the WNT Pathway. The American journal of pathology. 1999;154(2):515-23.

Alison MR, Lim SM, Nicholson LJ. Cancer stem cells: problems for therapy? The Journal of pathology. 2011;223(2):148-62.

Alvin A, Miller KI, Neilan BA. Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds. Microbiological research. 2014;169(7):483-95.

Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends in pharmacological sciences. 2009;30(2):85-94.

Shishodia S, Chaturvedi MM, Aggarwal BB. Role of curcumin in cancer therapy. Current problems in cancer. 2007;31(4):243-305.

Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer letters. 2008;267(1):133-64.

Nishiya N, Oku Y, Kumagai Y, Sato Y, Yamaguchi E, Sasaki A, et al. A zebrafish chemical suppressor screening identifies small molecule inhibitors of the Wnt/β-catenin pathway. Chemistry & biology. 2014;21(4):530-40.

Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(6):2073-87. e3.

Li Y, Zhang T. Targeting cancer stem cells by curcumin and clinical applications. Cancer letters. 2014;346(2):197-205.

Makoukji J, Grenier J, Liere P, Meffre D, Massaad C. Differential regulation of Wnt/beta-catenin signaling by Liver X Receptors in Schwann cells and oligodendrocytes. Biochemical pharmacology. 2013;86(1):106-14.

Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini K. Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochimica et Biophysica Acta (BBA)-General Subjects. 2008;1780(4):673-9.

Yan C, Jamaluddin MS, Aggarwal B, Myers J, Boyd DD. Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Molecular Cancer Therapeutics. 2005;4(2):233-41.

Prasad CP, Rath G, Mathur S, Bhatnagar D, Ralhan R. Potent growth suppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/β-catenin signaling. Chemico-biological interactions. 2009;181(2):263-71.

Chen F, Wang H, Xiang X, Yuan J, Chu W, Xue X, et al. Curcumin increased the differentiation rate of neurons in neural stem cells via wnt signaling in vitro study. Journal of Surgical Research. 2014;192(2):298-304.

Tiwari SK, Agarwal S, Seth B, Yadav A, Nair S, Bhatnagar P, et al. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer’s disease model via canonical Wnt/β-catenin pathway. ACS nano. 2013;8(1):76-103.

Torchilin V. Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. European Journal of Pharmaceutics and Biopharmaceutics. 2009;71(3):431-44.

Devadasu VR, Bhardwaj V, Kumar MR. Can controversial nanotechnology promise drug delivery? Chemical reviews. 2012;113(3):1686-735.

Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of controlled release. 2000;65(1):271-84.

Torchilin V. Tumor delivery of macromolecular drugs based on the EPR effect. Advanced drug delivery reviews. 2011;63(3):131-5.

Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clinical Cancer Research. 2001;7(7):1894-900.

Cheng A-L, Hsu C-H, Lin J-K, Hsu M-M, Ho Y-F, Shen T-S, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):2895-900.

Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, et al. Phase I clinical trial of oral curcumin. Clinical Cancer Research. 2004;10(20):6847-54.

Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiology and Prevention Biomarkers. 2005;14(1):120-5.

He Z-Y, Shi C-B, Wen H, Li F-L, Wang B-L, Wang J. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer investigation. 2011;29(3):208-13.

Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer prevention research. 2011;4(3):354-64.

Irving GR, Howells LM, Sale S, Kralj-Hans I, Atkin WS, Clark SK, et al. Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration—a clinical pilot study including assessment of patient acceptability. Cancer prevention research. 2013;6(2):119-28.

Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2004;287(1):G7-G17.

Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Alternative medicine review. 2009;14(2).

Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Digestive diseases and sciences. 2005;50(11):2191-3.

Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, Andoh A, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clinical Gastroenterology and Hepatology. 2006;4(12):1502-6.

Singla V, Mouli VP, Garg SK, Rai T, Choudhury BN, Verma P, et al. Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis—a randomized, placebo-controlled, pilot study. Journal of Crohn's and Colitis. 2014;8(3):208-14.

Guo D, Li Q, Lv Q, Wei Q, Cao S, Gu J. MiR-27a targets sFRP1 in hFOB cells to regulate proliferation, apoptosis and differentiation. PLoS One. 2014;9(3):e91354.

Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423(6938):448-52.

Yang VW. APC as a checkpoint gene: the beginning or the end? Gastroenterology. 2002;123(3):935-9.

Cong F, Schweizer L, Varmus H. Wnt signals across the plasma membrane to activate the β-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP. Development. 2004;131(20):5103-15.

He X, Semenov M, Tamai K, Zeng X. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: arrows point the way. Development. 2004;131(8):1663-77.

Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, et al. Constitutive transcriptional activation by a β-catenin-Tcf complex in APC−/− colon carcinoma. Science. 1997;275(5307):1784-7.

Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. β‐catenin is a target for the ubiquitin–proteasome pathway. The EMBO journal. 1997;16(13):3797-804.

Kitagawa M, Hatakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, et al. An F‐box protein, FWD1, mediates ubiquitin‐dependent proteolysis of β‐catenin. The EMBO journal. 1999;18(9):2401-10.

Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW. The SCFβ-TRCP–ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IκBα and β-catenin and stimulates IκBα ubiquitination in vitro. Genes & development. 1999;13(3):270-83.

Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P. Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3β. Current Biology. 1998;8(10):573-81.

Rubinfeld B, Albert I, Porfiri E, Fiol C. Binding of GSK3beta to teh APC-beta-catenin complex and regulation of complex assembly. Science. 1996;272(5264):1023.

Kishida S, Yamamoto H, Ikeda S, Kishida M, Sakamoto I, Koyama S, et al. Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of β-catenin. Journal of Biological Chemistry. 1998;273(18):10823-6.

Davidson G, Wu W, Shen J, Bilic J, Fenger U, Stannek P, et al. Casein kinase 1 γ couples Wnt receptor activation to cytoplasmic signal transduction. Nature. 2005;438(7069):867-72.

Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, et al. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature. 2005;438(7069):873-7.

Lee E, Salic A, Krüger R, Heinrich R, Kirschner MW. The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol. 2003;1(1):e10.

Cong F, Varmus H. Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of β-catenin. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(9):2882-7.

Brennan K, Gonzalez-Sancho JM, Castelo-Soccio LA, Howe LR, Brown AM. Truncated mutants of the putative Wnt receptor LRP6/Arrow can stabilize β-catenin independently of Frizzled proteins. Oncogene. 2004;23(28):4873-84.

Gao C, Chen Y-G. Dishevelled: The hub of Wnt signaling. Cellular signalling. 2010;22(5):717-27.

van Noort M, Clevers H. TCF transcription factors, mediators of Wnt-signaling in development and cancer. Developmental biology. 2002;244(1):1-8.

Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H, et al. Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature. 1998;395(6702):604-8.

Adachi S, Jigami T, Yasui T, Nakano T, Ohwada S, Omori Y, et al. Role of a BCL9-related β-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling. Cancer research. 2004;64(23):8496-501.

Belenkaya TY, Han C, Standley HJ, Lin X, Houston DW, Heasman J, et al. pygopus Encodes a nuclear protein essential for wingless/Wnt signaling. Development. 2002;129(17):4089-101.

Thompson B, Townsley F, Rosin-Arbesfeld R, Musisi H, Bienz M. A new nuclear component of the Wnt signalling pathway. Nature cell biology. 2002;4(5):367-73.

Townsley FM, Cliffe A, Bienz M. Pygopus and Legless target Armadillo/β-catenin to the nucleus to enable its transcriptional co-activator function. Nature cell biology. 2004;6(7):626-33.

He T-C, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, et al. Identification of c-MYC as a target of the APC pathway. Science. 1998;281(5382):1509-12.

Sansom OJ, Reed KR, van de Wetering M, Muncan V, Winton DJ, Clevers H, et al. Cyclin D1 is not an immediate target of β-catenin following Apc loss in the intestine. Journal of Biological Chemistry. 2005;280(31):28463-7.

Brabletz T, Jung A, Dag S, Hlubek F, Kirchner T. β-Catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. The American journal of pathology. 1999;155(4):1033-8.

Takahashi M, Tsunoda T, Seiki M, Nakamura Y, Furukawa Y. Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene. 2002;21(38):5861-7.

Hlubek F, Spaderna S, Jung A, Kirchner T, Brabletz T. β‐Catenin activates a coordinated expression of the proinvasive factors laminin‐5 γ2 chain and MT1‐MMP in colorectal carcinomas. International Journal of Cancer. 2004;108(2):321-6.

Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, et al. β-Catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell. 2002;111(2):251-63.

Batlle E, Bacani J, Begthel H, Jonkeer S, Gregorieff A, van de Born M, et al. EphB receptor activity suppresses colorectal cancer progression. Nature. 2005;435(7045):1126-30.

Herbst A, Bommer GT, Kriegl L, Jung A, Behrens A, Csanadi E, et al. ITF-2 is disrupted via allelic loss of chromosome 18q21, and ITF-2B expression is lost at the adenoma-carcinoma transition. Gastroenterology. 2009;137(2):639-48. e9.

Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Marsh JL, et al. β-catenin–sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nature genetics. 2001;28(1):53-7.

Roose J, Huls G, Van Beest M, Moerer P, Van Der Horn K, Goldschmeding R, et al. Synergy between tumor suppressor APC and the β-catenin-Tcf4 target Tcf1. Science. 1999;285(5435):1923-6.

Jho E-h, Zhang T, Domon C, Joo C-K, Freund J-N, Costantini F. Wnt/β-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Molecular and cellular biology. 2002;22(4):1172-83.

Leung JY, Kolligs FT, Wu R, Zhai Y, Kuick R, Hanash S, et al. Activation of AXIN2 Expression by β-Catenin-T Cell Factor A FEEDBACK REPRESSOR PATHWAY REGULATING Wnt SIGNALING. Journal of Biological Chemistry. 2002;277(24):21657-65.

Lustig B, Jerchow B, Sachs M, Weiler S, Pietsch T, Karsten U, et al. Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Molecular and cellular biology. 2002;22(4):1184-93.

Rousset R, Mack JA, Wharton KA, Axelrod JD, Cadigan KM, Fish MP, et al. Naked cuticle targets dishevelled to antagonize Wnt signal transduction. Genes & development. 2001;15(6):658-71.

Hao H-X, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012;485(7397):195-200.

Koo B-K, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012;488(7413):665-9.

Jiang X, Charlat O, Zamponi R, Yang Y, Cong F. Dishevelled promotes Wnt receptor degradation through recruitment of ZNRF3/RNF43 E3 ubiquitin ligases. Molecular cell. 2015;58(3):522-33.

De Lau WB, Snel B, Clevers HC. The R-spondin protein family. Genome biology. 2012;13(3):1.

Jin Y-R, Yoon JK. The R-spondin family of proteins: emerging regulators of WNT signaling. The international journal of biochemistry & cell biology. 2012;44(12):2278-87.

Peng WC, de Lau W, Forneris F, Granneman JC, Huch M, Clevers H, et al. Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5. Cell reports. 2013;3(6):1885-92.

Peng WC, de Lau W, Madoori PK, Forneris F, Granneman JC, Clevers H, et al. Structures of Wnt-antagonist ZNRF3 and its complex with R-spondin 1 and implications for signaling. PLoS One. 2013;8(12):e83110.

Wang D, Huang B, Zhang S, Yu X, Wu W, Wang X. Structural basis for R-spondin recognition by LGR4/5/6 receptors. Genes & development. 2013;27(12):1339-44.

Hao H-X, Jiang X, Cong F. Control of Wnt Receptor Turnover by R-spondin-ZNRF3/RNF43 Signaling Module and Its Dysregulation in Cancer. Cancers. 2016;8(6):54.

Van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annual review of physiology. 2009;71:241-60.

Umar S. Intestinal stem cells. Current gastroenterology reports. 2010;12(5):340-8.

Van der Flier LG, Sabates–Bellver J, Oving I, Haegebarth A, De Palo M, Anti M, et al. The intestinal Wnt/TCF signature. Gastroenterology. 2007;132(2):628-32.

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.

Schepers AG, Vries R, Van Den Born M, Van De Wetering M, Clevers H. Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes. The EMBO journal. 2011;30(6):1104-9.

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.

Muñoz 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. The EMBO journal. 2012;31(14):3079-91.

Koo B-K, van Es JH, van den Born M, Clevers H. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43; Znrf3-mutant neoplasia. Proceedings of the National Academy of Sciences. 2015;112(24):7548-50.

Van Limbergen J, Geddes K, Henderson P, Russell RK, Drummond HE, Satsangi J, et al. Paneth cell marker CD24 in NOD2 knockout organoids and in inflammatory bowel disease (IBD). Gut. 2013:gutjnl-2013-305077.

Zeilstra J, Joosten S, Van Andel H, Tolg C, Berns A, Snoek M, et al. Stem cell CD44v isoforms promote intestinal cancer formation in Apc (min) mice downstream of Wnt signaling. Oncogene. 2014;33(5):665-70.

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):2187-94. e1.

Levin TG, Powell AE, Davies PS, Silk AD, Dismuke AD, Anderson EC, et al. Characterization of the intestinal cancer stem cell marker CD166 in the human and mouse gastrointestinal tract. Gastroenterology. 2010;139(6):2072-82. e5.

Maria Cambuli F, Rezza A, Nadjar J, Plateroti M. Brief report: Musashi1‐eGFP mice, a new tool for differential isolation of the intestinal stem cell populations. Stem cells. 2013;31(10):2273-8.

Potten CS. Stem cells in gastrointestinal epithelium: numbers, characteristics and death. Philosophical Transactions of the Royal Society of London B: Biological Sciences. 1998;353(1370):821-30.

Sangiorgi E, Capecchi MR. Bmi1 is expressed in vivo in intestinal stem cells. Nature genetics. 2008;40(7):915-20.

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.

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. Proceedings of the National Academy of Sciences. 2011;108(1):179-84.

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.

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):1420-4.

Potten CS, Owen G, Booth D. Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci. 2002;115(11):2381-8.

Cui S, Chang P-Y. Current understanding concerning intestinal stem cells. World Journal of Gastroenterology. 2016;22(31):7099.

Gregorieff A, Pinto D, Begthel H, Destrée O, Kielman M, Clevers H. Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology. 2005;129(2):626-38.

Sato T, Clevers H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science. 2013;340(6137):1190-4.

Roth S, Fodde R. The nature of intestinal stem cells' nurture. EMBO reports. 2011;12(6):483-4.

Binnerts ME, Kim K-A, Bright JM, Patel SM, Tran K, Zhou M, et al. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proceedings of the National Academy of Sciences. 2007;104(37):14700-5.

van Es JH, Jay P, Gregorieff A, van Gijn ME, Jonkheer S, Hatzis P, et al. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nature cell biology. 2005;7(4):381-6.

Noren NK, Pasquale EB. Eph receptor–ephrin bidirectional signals that target Ras and Rho proteins. Cellular signalling. 2004;16(6):655-66.

Ohlstein B, Spradling A. Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling. Science. 2007;315(5814):988-92.

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.

Dick JE. Stem cell concepts renew cancer research. Blood. 2008;112(13):4793-807.

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.

Schmitt M, Metzger M, Gradl D, Davidson G, Orian-Rousseau V. CD44 functions in Wnt signaling by regulating LRP6 localization and activation. Cell Death & Differentiation. 2015;22(4):677-89.

Rappa G, Mercapide J, Anzanello F, Le TT, Johlfs MG, Fiscus RR, et al. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells. Experimental cell research. 2013;319(6):810-9.

Cojoc M, Peitzsch C, Kurth I, Trautmann F, Kunz-Schughart LA, Telegeev GD, et al. Aldehyde dehydrogenase is regulated by β-catenin/TCF and promotes radioresistance in prostate cancer progenitor cells. Cancer research. 2015;75(7):1482-94.

Chai R, Xia A, Wang T, Jan TA, Hayashi T, Bermingham-McDonogh O, et al. Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea. Journal of the Association for Research in Otolaryngology. 2011;12(4):455-69.

Kakarala M, Brenner DE, Korkaya H, Cheng C, Tazi K, Ginestier C, et al. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast cancer research and treatment. 2010;122(3):777-85.

Nautiyal J, Kanwar SS, Yu Y, Majumdar AP. Combination of dasatinib and curcumin eliminates chemo-resistant colon cancer cells. Journal of molecular signaling. 2011;6(1):7.

Yu Y, Kanwar SS, Patel BB, Nautiyal J, Sarkar FH, Majumdar AP. Elimination of colon cancer stem-like cells by the combination of curcumin and FOLFOX. Translational oncology. 2009;2(4):321-8.

Fong D, Yeh A, Naftalovich R, Choi TH, Chan MM. Curcumin inhibits the side population (SP) phenotype of the rat C6 glioma cell line: towards targeting of cancer stem cells with phytochemicals. Cancer letters. 2010;293(1):65-72.

Howells LM, Sale S, Sriramareddy SN, Irving GR, Jones DJ, Ottley CJ, et al. Curcumin ameliorates oxaliplatin‐induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo. International Journal of Cancer. 2011;129(2):476-86.

Kantara C, O'Connell M, Sarkar S, Moya S, Ullrich R, Singh P. Curcumin promotes autophagic survival of a subset of colon cancer stem cells, which are ablated by DCLK1-siRNA. Cancer research. 2014;74(9):2487-98.

Kim E, Davidson LA, Zoh RS, Hensel ME, Salinas ML, Patil BS, et al. Rapidly cycling Lgr5+ stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk. Cell Death & Disease. 2016;7(11):e2460.

Wang K, Zhang T, Liu L, Wang X, Wu P, Chen Z, et al. Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells. Int J Nanomedicine. 2012;7:4487-97.

Kanwar SS, Yu Y, Nautiyal J, Patel BB, Padhye S, Sarkar FH, et al. Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon cancer stem-like cells. Pharmaceutical research. 2011;28(4):827-38.


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