The role of the Wnt signaling pathway in cancer stem cells: prospects for drug development

References

• Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–111.
   PubMed Web of Science ®Google Scholar
• Gage FH, Temple S. Neural stem cells: generating and regenerating the brain. Neuron. 2013;80:588–601.
   PubMed Web of Science ®Google Scholar
• Cullen SM, Mayle A, Rossi L, Goodell MA. Hematopoietic stem cell development: an epigenetic journey. Curr Top Dev Biol. 2014;107:39–75.
   PubMed Web of Science ®Google Scholar
• Clevers H. The intestinal crypt, a prototype stem cell compartment. Cell. 2013;154:274–284.
   PubMed Web of Science ®Google Scholar
• Miki T, Yasuda SY, Kahn M. Wnt/beta-catenin signaling in embryonic stem cell self-renewal and somatic cell reprogramming. Stem Cell Rev. 2011;7:836–846.
   Web of Science ®Google Scholar
• Takahashi-Yanaga F, Kahn M. Targeting Wnt signaling: can we safely eradicate cancer stem cells? Clin Cancer Res. 2010;16:3153–3162.
   PubMed Web of Science ®Google Scholar
• Merchant AA, Matsui W. Targeting Hedgehog – a cancer stem cell pathway. Clin Cancer Res. 2010;16:3130–3140.
   PubMed Web of Science ®Google Scholar
• Liu J, Sato C, Cerletti M, Wagers A. Notch signaling in the regulation of stem cell self-renewal and differentiation. Curr Top Dev Biol. 2010;92:367–409.
   PubMed Web of Science ®Google Scholar
• Cohnheim J. Ueber entzuendung und eiterung [About inflammation and suppuration]. Path Anat Physiol Klin Med. 1867;40:1–79.
   Google Scholar
• Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755–768.
   PubMed Web of Science ®Google Scholar
• O’Brien CA, Kreso A, Jamieson CH. Cancer stem cells and self-renewal. Clin Cancer Res. 2010;16:3113–3120.
   PubMed Web of Science ®Google Scholar
• Armanios M, Greider CW. Telomerase and cancer stem cells. Cold Spring Harb Symp Quant Biol. 2005;70:205–208.
   PubMedGoogle Scholar
• Clevers H. The cancer stem cell: premises, promises and challenges. Nat Med. 2011;17:313–319.
   PubMed Web of Science ®Google Scholar
• Visvader JE, Lindeman GJ. Stem cells and cancer – the promise and puzzles. Mol Oncol. 2010;4:369–372.
   PubMed Web of Science ®Google Scholar
• Hussenet T, Dembélé D, Martinet N, Vignaud JM, du Manoir MS. An adult tissue-specific stem cell molecular phenotype is activated in epithelial cancer stem cells and correlated to patient outcome. Cell Cycle. 2010;9:321–327.
   PubMed Web of Science ®Google Scholar
• D’Angelo RC, Wicha MS. Stem cells in normal development and cancer. Prog Mol Biol Transl Sci. 2010;95:113–158.
   Web of Science ®Google Scholar
• Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A. Tumor growth need not be driven by rare cancer stem cells. Science. 2007; (3175836):337.
   Google Scholar
• Bruce WR, van der Gaag H. A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature. 1963;199:79–80.
   PubMed Web of Science ®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;3:730–737.
   PubMed Web of Science ®Google Scholar
• Jamieson CH, Weissman IL, Passegue E. Chronic versus acute myelogenous leukemia: a question of self-renewal. Cancer Cell. 2004;6:531–533.
   PubMed Web of Science ®Google Scholar
• Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.
   PubMed Web of Science ®Google Scholar
• Fang D, Nguyen TK, Leishear K, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 2005;65:9328–9337.
   PubMed Web of Science ®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;100:3983–3988.
   PubMed Web of Science ®Google Scholar
• Ma S, Chan KW, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132:2542–2556.
   PubMed Web of Science ®Google Scholar
• Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–1037.
   PubMed Web of Science ®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;445:106–110.
   PubMed Web of Science ®Google Scholar
• Akiyama T. Wnt/beta-catenin signaling. Cytokine Growth Factor Rev. 2000;11:273–282.
   PubMed Web of Science ®Google Scholar
• Niehrs C. The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol. 2012;13:767–779.
   PubMed Web of Science ®Google Scholar
• Veeman MT, Axelrod JD, Moon RT. A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell. 2003;5:367–377.
   PubMed Web of Science ®Google Scholar
• Mosimann C, Hausmann G, Basler K. Beta-catenin hits chromatin: regulation of Wnt target gene activation. Nat Rev Mol Cell Biol. 2009;10:276–286.
   PubMed Web of Science ®Google Scholar
• Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.
   PubMed Web of Science ®Google Scholar
• Moon RT, Kohn AD, De Ferrari GV, Kaykas A. WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet. 2004;5:691–701.
   PubMed Web of Science ®Google Scholar
• Thrasivoulou C, Millar M, Ahmed A. Activation of intracellular calcium by multiple Wnt ligands and translocation of beta-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/beta-catenin pathways. J Biol Chem. 2013;288:35651–35659.
   PubMed Web of Science ®Google Scholar
• Yamamoto S, Nishimura O, Misaki K, et al. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell. 2008;15:23–36.
   PubMed Web of Science ®Google Scholar
• Angers S, Moon RT. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol. 2009;10:468–477.
   PubMed Web of Science ®Google Scholar
• Lai SL, Chien AJ, Moon RT. Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis. Cell Res. 2009;19:532–545.
   PubMed Web of Science ®Google Scholar
• Alonso L, Fuchs E. Stem cells in the skin: waste not, Wnt not. Genes Dev. 2003;17:1189–1200.
   PubMed Web of Science ®Google Scholar
• Pinto D, Clevers H. Wnt control of stem cells and differentiation in the intestinal epithelium. Exp Cell Res. 2005;306:357–363.
   PubMed Web of Science ®Google Scholar
• Nemeth MJ, Mak KK, Yang Y, Bodine DM. Beta-Catenin expression in the bone marrow microenvironment is required for long-term maintenance of primitive hematopoietic cells. Stem Cells. 2009;27:1109–1119.
   PubMed Web of Science ®Google Scholar
• Malhotra S, Kincade PW. Wnt-related molecules and signaling pathway equilibrium in hematopoiesis. Cell Stem Cell. 2009;4:27–36.
   PubMed Web of Science ®Google Scholar
• Monga SP. Role of Wnt/beta-catenin signaling in liver metabolism and cancer. Int J Biochem Cell Biol. 2011;43:1021–1029.
   PubMed Web of Science ®Google Scholar
• Beers MF, Morrisey EE. The three R’s of lung health and disease: repair, remodeling, and regeneration. J Clin Invest. 2011;121:2065–2073.
   PubMed Web of Science ®Google Scholar
• Whyte JL, Smith AA, Helms JA. Wnt signaling and injury repair. Cold Spring Harb Perspect Biol. 2012;4:a008078.
   PubMed Web of Science ®Google Scholar
• Inestrosa NC, Arenas E. Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci. 2010;11:77–86.
   PubMed Web of Science ®Google Scholar
• 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;141:537–561.
   PubMedGoogle Scholar
• Lin SA, Barker N. Gastrointestinal stem cells in self-renewal and cancer. J Gastroenterol. 2011;46:1039–1055.
   Web of Science ®Google Scholar
• Anversa P, Leri A. Innate regeneration in the aging heart: healing from within. Mayo Clin Proc. 2013;88:871–883.
   Web of Science ®Google Scholar
• Williams A. Central nervous system regeneration – where are we? QJM. 2014;107(5):335–339.
   Web of Science ®Google Scholar
• Reya T, Duncan AW, Ailles L, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423:409–414.
   PubMed Web of Science ®Google Scholar
• Lindvall C, Zylstra CR, Evans N, et al. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development. PLoS One. 2009;4:e5813.
   Web of Science ®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;143:1518–1529.
   Web of Science ®Google Scholar
• Pinto D, Gregorieff A, Begthel H, Clevers H. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev. 2003;17:1709–1713.
   PubMed Web of Science ®Google Scholar
• Korinek V, Barker N, Moerer P, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet. 1998;19:379–383.
   PubMed Web of Science ®Google Scholar
• Tian H, Biehs B, Warming S, et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011;478:255–259.
   PubMed Web of Science ®Google Scholar
• Yan KS, Chia LA, Li X, et al. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc Natl Acad Sci U S A. 2012;109:466–471.
   PubMed Web of Science ®Google Scholar
• Barker N, van Es JH, Kuipers J, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–1007.
   PubMed Web of Science ®Google Scholar
• de Lau W, Barker N, Low TY, et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature. 2011;476:293–297.
   PubMed Web of Science ®Google Scholar
• Gregorieff A, Pinto D, Begthel H, Destree O, Kielman M, Clevers H. Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology. 2005;129:626–638.
   PubMed Web of Science ®Google Scholar
• Sato T, van Es JH, Snippert HJ, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469:415–418.
   PubMed Web of Science ®Google Scholar
• Bastide P, Darido C, Pannequin J, et al. Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium. J Cell Biol. 2007;178:635–648.
   PubMed Web of Science ®Google Scholar
• Mori-Akiyama Y, van den Born M, van Es JH, et al. SOX9 is required for the differentiation of paneth cells in the intestinal epithelium. Gastroenterology. 2007;133:539–546.
   PubMed Web of Science ®Google Scholar
• Willert K, Brown JD, Danenberg E, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423:448–452.
   PubMed Web of Science ®Google Scholar
• Fukuda S, Pelus LM. Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34(+) cells by hematopoietic growth factors: implication of survivin expression in normal hematopoiesis. Blood. 2001;98:2091–2100.
   PubMed Web of Science ®Google Scholar
• Leung CG, Xu Y, Mularski B, Liu H, Gurbuxani S, Crispino JD. Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells. J Exp Med. 2007;204:1603–1611.
   PubMed Web of Science ®Google Scholar
• Ma H, Nguyen C, Lee KS, Kahn M. Differential roles for the coactivators CBP and p300 on TCF/beta-catenin-mediated survivin gene expression. Oncogene. 2005;24:3619–3631.
   PubMed Web of Science ®Google Scholar
• Park E, Gang EJ, Hsieh YT, et al. Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia. Blood. 2011;118:2191–2199.
   PubMed Web of Science ®Google Scholar
• Gang EJ, Hsieh YT, Pham J, et al. Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia. Oncogene. 2014;33(17):2169–2178.
   PubMed Web of Science ®Google Scholar
• Zeng YA, Nusse R. Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture. Cell Stem Cell. 2010;6:568–577.
   PubMed Web of Science ®Google Scholar
• Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387–398.
   PubMed Web of Science ®Google Scholar
• Turashvili G, Bouchal J, Burkadze G, Kolar Z. Wnt signaling pathway in mammary gland development and carcinogenesis. Pathobiology. 2006;73:213–223.
   PubMed Web of Science ®Google Scholar
• Boras-Granic K, Wysolmerski JJ. Wnt signaling in breast organogenesis. Organogenesis. 2008;4:116–122.
   PubMedGoogle Scholar
• Imbert A, Eelkema R, Jordan S, Feiner H, Cowin P. Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland. J Cell Biol. 2001;153:555–568.
   PubMed Web of Science ®Google Scholar
• Liu BY, McDermott SP, Khwaja SS, Alexander CM. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc Natl Acad Sci U S A. 2004;101:4158–4163.
   PubMed Web of Science ®Google Scholar
• Tepera SB, McCrea PD, Rosen JM. A beta-catenin survival signal is required for normal lobular development in the mammary gland. J Cell Sci. 2003;116:1137–1149.
   PubMed Web of Science ®Google Scholar
• Hsu W, Shakya R, Costantini F. Impaired mammary gland and lymphoid development caused by inducible expression of Axin in transgenic mice. J Cell Biol. 2001;155:1055–1064.
   Web of Science ®Google Scholar
• Boras-Granic K, Chang H, Grosschedl R, Hamel PA. Lef1 is required for the transition of Wnt signaling from mesenchymal to epithelial cells in the mouse embryonic mammary gland. Dev Biol. 2006;295:219–231.
   PubMed Web of Science ®Google Scholar
• Alexander CM, Goel S, Fakhraldeen SA, Kim S. Wnt signaling in mammary glands: plastic cell fates and combinatorial signaling. Cold Spring Harb Perspect Biol. 2012;4(10):a008037.
   Web of Science ®Google Scholar
• Brennan KR, Brown AM. Wnt proteins in mammary development and cancer. J Mammary Gland Biol Neoplasia. 2004;9:119–131.
   PubMed Web of Science ®Google Scholar
• Kordon EC, Smith GH. An entire functional mammary gland may comprise the progeny from a single cell. Development. 1998;125:1921–1930.
   PubMed Web of Science ®Google Scholar
• Badders NM, Goel S, Clark RJ, et al. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage. PLoS One. 2009;4:e6594.
   PubMed Web of Science ®Google Scholar
• Klonisch T, Wiechec E, Hombach-Klonisch S, et al. Cancer stem cell markers in common cancers – therapeutic implications. Trends Mol Med. 2008;14:450–460.
   PubMed Web of Science ®Google Scholar
• Wielenga VJ, Smits R, Korinek V, et al. Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol. 1999;154:515–523.
   PubMed Web of Science ®Google Scholar
• Shulewitz M, Soloviev I, Wu T, Koeppen H, Polakis P, Sakanaka C. Repressor roles for TCF-4 and Sfrp1 in Wnt signaling in breast cancer. Oncogene. 2006;25:4361–4369.
   Web of Science ®Google Scholar
• Katoh Y, Katoh M. Comparative genomics on PROM1 gene encoding stem cell marker CD133. Int J Mol Med. 2007;19:967–970.
   Web of Science ®Google Scholar
• Yamada T, Takaoka AS, Naishiro Y, et al. Transactivation of the multidrug resistance 1 gene by T-cell factor 4/beta-catenin complex in early colorectal carcinogenesis. Cancer Res. 2000;60:4761–4766.
   PubMed Web of Science ®Google Scholar
• Corrêa S, Binato R, Du Rocher B, Castelo-Branco MT, Pizzatti L, Abdelhay E. Wnt/beta-catenin pathway regulates ABCB1 transcription in chronic myeloid leukemia. BMC Cancer. 2012;12:303.
   Web of Science ®Google Scholar
• Munz M, Baeuerle PA, Gires O. The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res. 2009;69:5627–5629.
   PubMed Web of Science ®Google Scholar
• Yamashita T, Budhu A, Forgues M, Wang XW. Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res. 2007;67:10831–10839.
   PubMed Web of Science ®Google Scholar
• Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982;31:99–109.
   PubMed Web of Science ®Google Scholar
• Sandberg CJ, Altschuler G, Jeong J, et al. Comparison of glioma stem cells to neural stem cells from the adult human brain identifies dysregulated Wnt-signaling and a fingerprint associated with clinical outcome. Exp Cell Res. 2013;319:2230–2243.
   Web of Science ®Google Scholar
• Zhang Y, Toy KA, Kleer CG. Metaplastic breast carcinomas are enriched in markers of tumor-initiating cells and epithelial to mesenchymal transition. Mod Pathol. 2012;25:178–184.
   Web of Science ®Google Scholar
• DiMeo TA, Anderson K, Phadke P, et al. A novel lung metastasis signature links Wnt signaling with cancer cell self-renewal and epithelial-mesenchymal transition in basal-like breast cancer. Cancer Res. 2009;69:5364–5373.
   PubMedGoogle Scholar
• Howe LR, Watanabe O, Leonard J, Brown AM. Twist is up-regulated in response to Wnt1 and inhibits mouse mammary cell differentiation. Cancer Res. 2003;63:1906–1913.
   PubMed Web of Science ®Google Scholar
• Takebe N, Warren RQ, Ivy SP. Breast cancer growth and metastasis: interplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition. Breast Cancer Res. 2011;13:211.
   PubMed Web of Science ®Google Scholar
• Bhat-Nakshatri P, Appaiah H, Ballas C, et al. SLUG/SNAI2 and tumor necrosis factor generate breast cells with CD44+/CD24− phenotype. BMC Cancer. 2010;10:411.
   Web of Science ®Google Scholar
• Moreno-Bueno G, Portillo F, Cano A. Transcriptional regulation of cell polarity in EMT and cancer. Oncogene. 2008;27:6958–6969.
   PubMed Web of Science ®Google Scholar
• Conacci-Sorrell M, Simcha I, Ben-Yedidia T, Blechman J, Savagner P, Ben-Ze’ev A. Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. J Cell Biol. 2003;163:847–857.
   PubMed Web of Science ®Google Scholar
• Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–715.
   PubMed Web of Science ®Google Scholar
• Brabletz T, Hlubek F, Spaderna S, et al. Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs. 2005;179:56–65.
   PubMed Web of Science ®Google Scholar
• Wang J, O’Bara MA, Pol SU, Sim FJ. CD133/CD140a-based isolation of distinct human multipotent neural progenitor cells and oligodendrocyte progenitor cells. Stem Cells Dev. 2013;22:2121–2131.
   Web of Science ®Google Scholar
• Shmelkov SV, St Clair R, Lyden D, Rafii S. AC133/CD133/Prominin-1. Int J Biochem Cell Biol. 2005;37:715–719.
   PubMed Web of Science ®Google Scholar
• Corbeil D, Marzesco AM, Wilsch-Brauninger M, Huttner WB. The intriguing links between prominin-1 (CD133), cholesterol-based membrane microdomains, remodeling of apical plasma membrane protrusions, extracellular membrane particles, and (neuro)epithelial cell differentiation. FEBS Lett. 2010;584:1659–1664.
   PubMed Web of Science ®Google Scholar
• Yin AH, Miraglia S, Zanjani ED, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997;90:5002–5012.
   PubMed Web of Science ®Google Scholar
• Vermeulen L, Todaro M, de Sousa Mello F, et al. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci U S A. 2008;105:13427–13432.
   PubMed Web of Science ®Google Scholar
• Uchida H, Yamazaki K, Fukuma M, et al. Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer. Cancer Sci. 2010;101:1731–1737.
   PubMed Web of Science ®Google Scholar
• Haraguchi N, Utsunomiya T, Inoue H, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells. 2006;24:506–513.
   PubMed Web of Science ®Google Scholar
• Hirschmann-Jax C, Foster AE, Wulf GG, Goodell MA, Brenner MK. A distinct “side population” of cells in human tumor cells: implications for tumor biology and therapy. Cell Cycle. 2005;4:203–205.
   PubMed Web of Science ®Google Scholar
• Moshaver B, van Rhenen A, Kelder A, et al. Identification of a small subpopulation of candidate leukemia-initiating cells in the side population of patients with acute myeloid leukemia. Stem Cells. 2008;26:3059–3067.
   PubMed Web of Science ®Google Scholar
• Wang Y, Krivtsov AV, Sinha AU, et al. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science. 2010;327:1650–1653.
   PubMed Web of Science ®Google Scholar
• Heidel FH, Bullinger L, Feng Z, et al. Genetic and pharmacologic inhibition of beta-catenin targets imatinib-resistant leukemia stem cells in CML. Cell Stem Cell. 2012;10:412–424.
   PubMed Web of Science ®Google Scholar
• Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci U S A. 2006;103:2794–2799.
   PubMed Web of Science ®Google Scholar
• Pehlivan M, Sercan Z, Sercan HO. sFRP1 promoter methylation is associated with persistent Philadelphia chromosome in chronic myeloid leukemia. Leuk Res. 2009;33:1062–1067.
   PubMed Web of Science ®Google Scholar
• Holland JD, Klaus A, Garratt AN, Birchmeier W. Wnt signaling in stem and cancer stem cells. Curr Opin Cell Biol. 2013;25:254–264.
   PubMed Web of Science ®Google Scholar
• Polakis P. Drugging Wnt signalling in cancer. EMBO J. 2012;31:2737–2746.
   PubMed Web of Science ®Google Scholar
• Anastas JN, Moon RT. WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 2013;13:11–26.
   PubMed Web of Science ®Google Scholar
• Groden J, Thliveris A, Samowitz W, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991;66:589–600.
   PubMed Web of Science ®Google Scholar
• Kinzler KW, Nilbert MC, Su LK, et al. Identification of FAP locus genes from chromosome 5q21. Science. 1991;253:661–665.
   PubMed Web of Science ®Google Scholar
• Bodmer WF. Cancer genetics: colorectal cancer as a model. J Hum Genet. 2006;51:391–396.
   Web of Science ®Google Scholar
• Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev. 2007;17:45–51.
   PubMed Web of Science ®Google Scholar
• Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998;396:643–649.
   PubMed Web of Science ®Google Scholar
• Clements WM, Lowy AM, Groden J. Adenomatous polyposis coli/beta-catenin interaction and downstream targets: altered gene expression in gastrointestinal tumors. Clin Colorectal Cancer. 2003;3:113–120.
   PubMedGoogle Scholar
• Drier Y, Lawrence MS, Carter SL, et al. Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability. Genome Res. 2013;23:228–235.
   Web of Science ®Google Scholar
• Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P. Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science. 1997;275:1790–1792.
   PubMed Web of Science ®Google Scholar
• Herr P, Hausmann G, Basler K. WNT secretion and signalling in human disease. Trends Mol Med. 2012;18:483–493.
   Web of Science ®Google Scholar
• Han ZG. Functional genomic studies: insights into the pathogenesis of liver cancer. Annu Rev Genomics Hum Genet. 2012;13:171–205.
   PubMed Web of Science ®Google Scholar
• Sastre-Perona A, Santisteban P. Role of the wnt pathway in thyroid cancer. Front Endocrinol (Lausanne). 2012;3:31.
   PubMedGoogle Scholar
• Gatcliffe TA, Monk BJ, Planutis K, Holcombe RF. Wnt signaling in ovarian tumorigenesis. Int J Gynecol Cancer. 2008;18:954–962.
   PubMed Web of Science ®Google Scholar
• Caldwell GM, Jones C, Gensberg K, et al. The Wnt antagonist sFRP1 in colorectal tumorigenesis. Cancer Res. 2004;64:883–888.
   PubMed Web of Science ®Google Scholar
• Lee AY, He B, You L, et al. Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma. Oncogene. 2004;23:6672–6676.
   PubMed Web of Science ®Google Scholar
• Suzuki H, Watkins DN, Jair KW, et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 2004;36:417–422.
   PubMed Web of Science ®Google Scholar
• Fukui T, Kondo M, Ito G, et al. Transcriptional silencing of secreted frizzled related protein 1 (SFRP 1) by promoter hypermethylation in non-small-cell lung cancer. Oncogene. 2005;24:6323–6327.
   PubMed Web of Science ®Google Scholar
• Zou H, Molina JR, Harrington JJ, et al. Aberrant methylation of secreted frizzled-related protein genes in esophageal adenocarcinoma and Barrett’s esophagus. Int J Cancer. 2005;116:584–591.
   PubMed Web of Science ®Google Scholar
• Rhee CS, Sen M, Lu D, et al. Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas. Oncogene. 2002;21:6598–6605.
   PubMed Web of Science ®Google Scholar
• Wong SC, Lo SF, Lee KC, Yam JW, Chan JK, Wendy Hsiao WL. Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours. J Pathol. 2002;196:145–153.
   PubMed Web of Science ®Google Scholar
• Milovanovic T, Planutis K, Nguyen A, et al. Expression of Wnt genes and frizzled 1 and 2 receptors in normal breast epithelium and infiltrating breast carcinoma. Int J Oncol. 2004;25:1337–1342.
   Web of Science ®Google Scholar
• Okino K, Nagai H, Hatta M, et al. Up-regulation and overproduction of DVL-1, the human counterpart of the Drosophila dishevelled gene, in cervical squamous cell carcinoma. Oncol Rep. 2003;10:1219–1223.
   PubMed Web of Science ®Google Scholar
• Uematsu K, Kanazawa S, You L, et al. Wnt pathway activation in mesothelioma: evidence of Dishevelled overexpression and transcriptional activity of beta-catenin. Cancer Res. 2003;63:4547–4551.
   PubMed Web of Science ®Google Scholar
• Uematsu K, He B, You L, Xu Z, McCormick F, Jablons DM. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene. 2003;22:7218–7221.
   PubMed Web of Science ®Google Scholar
• Grosch S, Tegeder I, Niederberger E, Brautigam L, Geisslinger G. COX-2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX-2 inhibitor celecoxib. FASEB J. 2001;15:2742–2744.
   PubMed Web of Science ®Google Scholar
• Maier TJ, Janssen A, Schmidt R, Geisslinger G, Grosch S. Targeting the beta-catenin/APC pathway: a novel mechanism to explain the cyclooxygenase-2-independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. FASEB J. 2005;19:1353–1355.
   PubMed Web of Science ®Google Scholar
• Sakoguchi-Okada N, Takahashi-Yanaga F, Fukada K, et al. Celecoxib inhibits the expression of survivin via the suppression of promoter activity in human colon cancer cells. Biochem Pharmacol. 2007;73:1318–1329.
   PubMed Web of Science ®Google Scholar
• Takahashi-Yanaga F, Yoshihara T, Jingushi K, et al. Celecoxib-induced degradation of T-cell factors-1 and -4 in human colon cancer cells. Biochem Biophys Res Commun. 2008;377:1185–1190.
   Web of Science ®Google Scholar
• Shah S, Hecht A, Pestell R, Byers SW. Trans-repression of beta-catenin activity by nuclear receptors. J Biol Chem. 2003;278:48137–48145.
   PubMed Web of Science ®Google Scholar
• Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348:891–899.
   PubMed Web of Science ®Google Scholar
• Sandler RS, Halabi S, Baron JA, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med. 2003;348:883–890.
   PubMed Web of Science ®Google Scholar
• Phillips RK, Wallace MH, Lynch PM, 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;50:857–860.
   PubMed Web of Science ®Google Scholar
• Jiang Y, Prunier C, Howe PH. The inhibitory effects of Disabled-2 (Dab2) on Wnt signaling are mediated through Axin. Oncogene. 2008;27:1865–1875.
   Web of Science ®Google Scholar
• Palmer HG, Gonzalez-Sancho JM, Espada J, et al. Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol. 2001;154:369–387.
   PubMed Web of Science ®Google Scholar
• Kim J, Zhang X, Rieger-Christ KM, et al. Suppression of Wnt signaling by the green tea compound (−)-epigallocatechin 3-gallate (EGCG) in invasive breast cancer cells. Requirement of the transcriptional repressor HBP1. J Biol Chem. 2006;281:10865–10875.
   PubMed Web of Science ®Google Scholar
• Rao CV, Desai D, Rivenson A, Simi B, Amin S, Reddy BS. Chemoprevention of colon carcinogenesis by phenylethyl-3-methylcaffeate. Cancer Res. 1995;55:2310–2315.
   PubMed Web of Science ®Google Scholar
• Jaiswal AS, Marlow BP, Gupta N, Narayan S. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene. 2002;21:8414–8427.
   PubMed Web of Science ®Google Scholar
• Roccaro AM, Leleu X, Sacco A, et al. Resveratrol exerts antiproliferative activity and induces apoptosis in Waldenstrom’s macroglobulinemia. Clin Cancer Res. 2008;14:1849–1858.
   PubMed Web of Science ®Google Scholar
• Morris HR, Taylor GW, Masento MS, Jermyn KA, Kay RR. Chemical structure of the morphogen differentiation inducing factor from Dictyostelium discoideum. Nature. 1987;328:811–814.
   PubMed Web of Science ®Google Scholar
• Mori J, Takahashi-Yanaga F, Miwa Y, et al. Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr286 in squamous cell carcinoma. Exp Cell Res. 2005;310:426–433.
   Web of Science ®Google Scholar
• Chimura T, Launey T, Ito M. Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif. BMC Genomics. 2011;12:300.
   PubMed Web of Science ®Google Scholar
• Huang SM, Mishina YM, Liu S, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009;461:614–620.
   PubMed Web of Science ®Google Scholar
• Kadowaki T, Wilder E, Klingensmith J, Zachary K, Perrimon N. The segment polarity gene porcupine encodes a putative multitransmembrane protein involved in Wingless processing. Genes Dev. 1996;10:3116–3128.
   PubMed Web of Science ®Google Scholar
• Voronkov A, Krauss S. Wnt/beta-catenin signaling and small molecule inhibitors. Curr Pharm Des. 2013;19:634–664.
   PubMed Web of Science ®Google Scholar
• Heidel FH, Mar BG, Armstrong SA. Self-renewal related signaling in myeloid leukemia stem cells. Int J Hematol. 2011;94:109–117.
   PubMed Web of Science ®Google Scholar
• Jiang X, Hao HX, Growney JD, et al. Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A. 2013;110:12649–12654.
   PubMed Web of Science ®Google Scholar
• Hofmann K. A superfamily of membrane-bound O-acyltransferases with implications for wnt signaling. Trends Biochem Sci. 2000;25:111–112.
   PubMed Web of Science ®Google Scholar
• Gurney A, Axelrod F, Bond CJ, et al. Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors. Proc Natl Acad Sci U S A. 2012;109:11717–11722.
   PubMed Web of Science ®Google Scholar
• Smith DC, Rosen LS Chugh R, et al. First-in-human evaluation of the human monoclonal antibody vantictumab (OMP-18R5; anti-Frizzled) targeting the WNT pathway in a phase I study for patients with advanced solid tumors. In: Abstracts of the 2014 Conference of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 2540.
   Google Scholar
• Smith DC, Wells Messersmith MG, Chugh R, et al. A first-in-human Phase 1 study of anti-cancer stem cell (CSC) agent OMP-54F28 (FZD8-Fc) targeting the WNT pathway in patients with advanced solid tumors. In: Abstracts of the 104th Conference of the American Association of Cancer Research; April 6–10, 2013; Washington, DC. Abstract B79.
   Google Scholar
• Emami KH, Nguyen C, Ma H, et al. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proc Natl Acad Sci U S A. 2004;101:12682–12687.
   PubMed Web of Science ®Google Scholar
• McMillan M, Kahn M. Investigating Wnt signaling: a chemogenomic safari. Drug Discov Today. 2005;10:1467–1474.
   PubMed Web of Science ®Google Scholar
• El-Khoueiry AB, Ning Y, Yang D, et al. A phase I first-in-human study of PRI-724 in patients (pts) with advanced solid tumors. In: Abstracts of the 2014 Conference of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 2501.
   Google Scholar
• Liu J, Pan S, Hsieh MH, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 2013;110:20224–20229.
   PubMed Web of Science ®Google Scholar