Skip to main content
SpringerLink
Log in

An Oncogenic Hub: β-Catenin as a Molecular Target for Cancer Therapeutics

  • Chapter
Protein-Protein Interactions as New Drug Targets

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 186))

Abstract

The Wnt/β-catenin signaling pathway plays diverse roles in embryonic development and in maintenance of organs and tissues in adults. Activation of this signaling cascade inhibits degradation of the pivotal component β-catenin, which in turn stimulates transcription of downstream target genes. Over the past two decades, intensive worldwide investigations have yielded considerable progress toward understanding the cellular and molecular mechanisms of Wnt signaling and its involvement in the pathogenesis of a range of human diseases. Remarkably, β-catenin signaling is aberrantly activated in greater than 70% of colorectal cancers and to a lesser extent in other tumor types, promoting cancer cell proliferation, survival and migration. Accordingly, β-catenin has gained recognition as an enticing molecular target for cancer therapeutics. Disruption of protein-protein interactions essential for β-catenin activity holds immense promise for the development of novel anti-cancer drugs. In this review, we focus on the regulation of β-catenin-dependent transcriptional activation and discuss potential therapeutic opportunities to block this signaling pathway in cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aoki M, Hecht A, Kruse U, Kemler R, Vogt PK (1999) Nuclear endpoint of Wnt signaling: neoplastic transformation induced by transactivating lymphoid-enhancing factor 1. Proc Natl Acad Sci USA 96:139–144

    Article  PubMed  CAS  Google Scholar 

  • Arce L, Yokoyama NN, Waterman ML (2006) Diversity of LEF/TCF action in development and disease. Oncogene 25:7492–7504

    Article  PubMed  CAS  Google Scholar 

  • Barker N, Hurlstone A, Musisi H, Miles A, Bienz M, Clevers H (2001) The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation. EMBO J 20:4935–4943

    Article  PubMed  CAS  Google Scholar 

  • Bauer A, Huber O, Kemler R (1998) Pontin52, an interaction partner of beta-catenin, binds to the TATA box binding protein. Proc Natl Acad Sci USA 95:14787–14792

    Article  PubMed  CAS  Google Scholar 

  • Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J (2000) Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J 19:6121–6130

    Article  PubMed  CAS  Google Scholar 

  • Beachy PA, Karhadkar SS, Berman DM (2004) Tissue repair and stem cell renewal in carcinogenesis. Nature 432:324–331

    Article  PubMed  CAS  Google Scholar 

  • Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C, Wirtz R, Kuhl M, Wedlich D, Birchmeier W (1998) Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science 280:596–599

    Article  PubMed  CAS  Google Scholar 

  • Belenkaya TY, Han C, Standley HJ, Lin X, Houston DW, Heasman J, Lin X (2002) pygopus Encodes a nuclear protein essential for wingless/Wnt signaling. Development 129:4089–4101

    PubMed  CAS  Google Scholar 

  • Bienz M, Clevers H (2003) Armadillo/beta-catenin signals in the nucleus – proof beyond a reasonable doubt? Nat Cell Biol 5:179–182

    Article  PubMed  CAS  Google Scholar 

  • Bos CL, Kodach LL, van den Brink GR, Diks SH, van Santen MM, Richel DJ, Peppelenbosch MP, Hardwick JC (2006) Effect of aspirin on the Wnt/beta-catenin pathway is mediated via protein phosphatase 2A. Oncogene 25:6447–6456

    Article  PubMed  CAS  Google Scholar 

  • Brannon M, Brown JD, Bates R, Kimelman D, Moon RT (1999) XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development. Development 126:3159–3170

    PubMed  CAS  Google Scholar 

  • Cadigan KM, Liu YI (2006) Wnt signaling: complexity at the surface. J Cell Sci 119:395–402

    Article  PubMed  CAS  Google Scholar 

  • Cadigan KM, Nusse R (1997) Wnt signaling: a common theme in animal development. Genes Dev 11:3286–3305

    Article  PubMed  CAS  Google Scholar 

  • Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, Simonds WF, Gillanders EM, Kennedy AM, Chen JD, Agarwal SK, Sood R, Jones MP, Moses TY, Haven C, Petillo D, Leotlela PD, Harding B, Cameron D, Pannett AA, Hoog A, Heath H, 3rd, James-Newton LA, Robinson B, Zarbo RJ, Cavaco BM, Wassif W, Perrier ND, Rosen IB, Kristoffersson U, Turnpenny PD, Farnebo LO, Besser GM, Jackson CE, Morreau H, Trent JM, Thakker RV, Marx SJ, Teh BT, Larsson C, Hobbs MR (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 32:676–680

    Article  PubMed  CAS  Google Scholar 

  • Castano J, Raurell I, Piedra JA, Miravet S, Dunach M, Garcia de Herreros A (2002) Beta-catenin N- and C-terminal tails modulate the coordinated binding of adherens junction proteins to beta-catenin. J Biol Chem 277:31541–31550

    Article  PubMed  CAS  Google Scholar 

  • Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science 310:1504–1510

    Article  PubMed  CAS  Google Scholar 

  • Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H, Peifer M, Bejsovec A (1998) Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395:604–608

    Article  PubMed  CAS  Google Scholar 

  • Choi HJ, Huber AH, Weis WI (2006) Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity. J Biol Chem 281:1027–1038

    Article  PubMed  CAS  Google Scholar 

  • Clarke AR (2006) Wnt signalling in the mouse intestine. Oncogene 25:7512–7521

    Article  PubMed  CAS  Google Scholar 

  • Clevers H (2006a) Colon cancer – understanding how NSAIDs work. N Engl J Med 354:761–773

    Article  PubMed  CAS  Google Scholar 

  • Clevers H (2006b) Wnt/beta-catenin signaling in development and disease. Cell 127:469–480

    Article  PubMed  CAS  Google Scholar 

  • Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze’ev A (2002) Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev 16:2058–2072

    Article  PubMed  CAS  Google Scholar 

  • Cong F, Zhang J, Pao W, Zhou P, Varmus H (2003) A protein knockdown strategy to study the function of beta-catenin in tumorigenesis. BMC Mol Biol 4:10

    Article  PubMed  Google Scholar 

  • Courey AJ, Jia S (2001) Transcriptional repression: the long and the short of it. Genes Dev 15:2786–2796

    PubMed  CAS  Google Scholar 

  • Crawford HC, Fingleton BM, Rudolph-Owen LA, Goss KJ, Rubinfeld B, Polakis P, Matrisian LM (1999) The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene 18:2883–2891

    Article  PubMed  CAS  Google Scholar 

  • Daniels DL, Weis WI (2002) ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules. Mol Cell 10:573–584

    Article  PubMed  CAS  Google Scholar 

  • Daniels DL, Weis WI (2005) Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nat Struct Mol Biol 12:364–371

    Article  PubMed  CAS  Google Scholar 

  • Davidson G, Wu W, Shen J, Bilic J, Fenger U, Stannek P, Glinka A, Niehrs C (2005) Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction. Nature 438:867–872

    Article  PubMed  CAS  Google Scholar 

  • de La Coste A, Romagnolo B, Billuart P, Renard CA, Buendia MA, Soubrane O, Fabre M, Chelly J, Beldjord C, Kahn A, Perret C (1998) Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Natl Acad Sci USA 95: 8847–8851

    Article  Google Scholar 

  • Dihlmann S, Klein S, Doeberitz Mv MK (2003) Reduction of beta-catenin/T-cell transcription factor signaling by aspirin and indomethacin is caused by an increased stabilization of phosphorylated beta-catenin. Mol Cancer Ther 2:509–516

    PubMed  CAS  Google Scholar 

  • Easwaran V, Pishvaian M, Salimuddin, Byers S (1999) Cross-regulation of beta-catenin-LEF/TCF and retinoid signaling pathways. Curr Biol 9:1415–1418

    Article  PubMed  CAS  Google Scholar 

  • Eguchi M, Nguyen C, Lee SC, Kahn M (2005) ICG-001, a novel small molecule regulator of TCF/beta-catenin transcription. Med Chem 1:467–472

    Article  PubMed  CAS  Google Scholar 

  • Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL, Kim HY, Moon SH, Ha JR, Kahn M (2004) A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proc Natl Acad Sci USA 101:12682–12687

    Article  PubMed  CAS  Google Scholar 

  • Feng Y, Lee N, Fearon ER (2003) TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res 63:8726–8734

    PubMed  CAS  Google Scholar 

  • Gad S, Teboul D, Lievre A, Goasguen N, Berger A, Beaune P, Laurent-Puig P (2004) Is the gene encoding Chibby implicated as a tumour suppressor in colorectal cancer ? BMC Cancer 4:31

    Article  PubMed  CAS  Google Scholar 

  • Gamallo C, Palacios J, Moreno G, Calvo de Mora J, Suarez A, Armas A (1999) Beta-catenin expression pattern in stage I and II ovarian carcinomas: relationship with beta-catenin gene mutations, clinicopathological features, and clinical outcome. Am J Pathol 155:527–536

    PubMed  CAS  Google Scholar 

  • Gates J, Peifer M (2005) Can 1, 000 reviews be wrong? Actin, alpha-Catenin, and adherens junctions. Cell 123:769–772

    Article  PubMed  CAS  Google Scholar 

  • Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJ (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328:1313–1316

    Article  PubMed  CAS  Google Scholar 

  • Giles RH, van Es JH, Clevers H (2003) Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 1653:1–24

    PubMed  CAS  Google Scholar 

  • Giovannucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, Speizer FE (1995) Aspirin and the risk of colorectal cancer in women. N Engl J Med 333:609–614

    Article  PubMed  CAS  Google Scholar 

  • Goodman RH, Smolik S (2000) CBP/p300 in cell growth, transformation, and development. Genes Dev 14:1553–1577

    PubMed  CAS  Google Scholar 

  • Gottardi CJ, Gumbiner BM (2004) Role for ICAT in beta-catenin-dependent nuclear signaling and cadherin functions. Am J Physiol Cell Physiol 286:C747–C756

    Article  PubMed  CAS  Google Scholar 

  • Graham TA, Weaver C, Mao F, Kimelman D, Xu W (2000) Crystal structure of a beta-catenin/Tcf complex. Cell 103:885–896

    Article  PubMed  CAS  Google Scholar 

  • Graham TA, Ferkey DM, Mao F, Kimelman D, Xu W (2001) Tcf4 can specifically recognize beta-catenin using alternative conformations. Nat Struct Biol 8:1048–1052

    Article  PubMed  CAS  Google Scholar 

  • Graham TA, Clements WK, Kimelman D, Xu W (2002) The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT. Mol Cell 10:563–571

    Article  PubMed  CAS  Google Scholar 

  • Greaves S (2003) Small changes in Wnt signalling. Nat Cell Biol 5:387

    Article  PubMed  CAS  Google Scholar 

  • Green DW, Roh H, Pippin JA, Drebin JA (2001) Beta-catenin antisense treatment decreases beta-catenin expression and tumor growth rate in colon carcinoma xenografts. J Surg Res 101:16–20

    Article  PubMed  CAS  Google Scholar 

  • Gregorieff A, Pinto D, Begthel H, Destree O, Kielman M, Clevers H (2005) Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 129:626–638

    PubMed  CAS  Google Scholar 

  • Grosch S, Maier TJ, Schiffmann S, Geisslinger G (2006) Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst 98:736–747

    Article  PubMed  CAS  Google Scholar 

  • Ha NC, Tonozuka T, Stamos JL, Choi HJ, Weis WI (2004) Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation. Mol Cell 15:511–521

    Article  PubMed  CAS  Google Scholar 

  • Harada N, Tamai Y, Ishikawa T, Sauer B, Takaku K, Oshima M, Taketo MM (1999) Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J 18:5931–5942

    Article  PubMed  CAS  Google Scholar 

  • Hawcroft G, D’Amico M, Albanese C, Markham AF, Pestell RG, Hull MA (2002) Indomethacin induces differential expression of beta-catenin, gamma-catenin and T-cell factor target genes in human colorectal cancer cells. Carcinogenesis 23:107–114

    Article  PubMed  CAS  Google Scholar 

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512

    Article  PubMed  CAS  Google Scholar 

  • He B, Reguart N, You L, Mazieres J, Xu Z, Lee AY, Mikami I, McCormick F, Jablons DM (2005) Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations. Oncogene 24:3054–3058

    Article  PubMed  CAS  Google Scholar 

  • Hecht A, Litterst CM, Huber O, Kemler R (1999) Functional characterization of multiple transactivating elements in beta-catenin, some of which interact with the TATA-binding protein in vitro. J Biol Chem 274:18017–18025

    Article  PubMed  CAS  Google Scholar 

  • Hecht A, Vleminckx K, Stemmler MP, van Roy F, Kemler R (2000) The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO J 19:1839–1850

    Article  PubMed  CAS  Google Scholar 

  • Hoang B, Moos M Jr, Vukicevic S, Luyten FP (1996) Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis. J Biol Chem 271:26131–26137

    Article  PubMed  CAS  Google Scholar 

  • Hoffmans R, Basler K (2004) Identification and in vivo role of the Armadillo-Legless interaction. Development 131:4393–4400

    Article  PubMed  CAS  Google Scholar 

  • Hoffmans R, Stadeli R, Basler K (2005) Pygopus and legless provide essential transcriptional coactivator functions to armadillo/beta-catenin. Curr Biol 15:1207–1211

    Article  PubMed  CAS  Google Scholar 

  • Hoppler S, Kavanagh CL (2007) Wnt signalling: variety at the core. J Cell Sci 120:385–393

    Article  PubMed  CAS  Google Scholar 

  • Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence Marsh J, Holcombe RF, Waterman ML (2001) Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nat Genet 28:53–57

    Article  PubMed  CAS  Google Scholar 

  • Hsieh JC, Kodjabachian L, Rebbert ML, Rattner A, Smallwood PM, Samos CH, Nusse R, Dawid IB, Nathans J (1999) A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature 398:431–496

    Article  PubMed  CAS  Google Scholar 

  • Hsu SC, Galceran J, Grosschedl R (1998) Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin. Mol Cell Biol 18:4807–4818

    PubMed  CAS  Google Scholar 

  • Huber AH, Weis WI (2001) The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin. Cell 105:391–402

    Article  PubMed  CAS  Google Scholar 

  • Huber AH, Nelson WJ, Weis WI (1997) Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell 90:871–882

    Article  PubMed  CAS  Google Scholar 

  • Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F (2002) Wnt/beta-catenin/Tcf signaling induces the transcription of axin2, a negative regulator of the signaling pathway. Mol Cell Biol 22:1172–1183

    Article  PubMed  CAS  Google Scholar 

  • Jolly K, Cheng KK, Langman MJ (2002) NSAIDs and gastrointestinal cancer prevention. Drugs 62:945–956

    Article  PubMed  CAS  Google Scholar 

  • Kanemaki M, Makino Y, Yoshida T, Kishimoto T, Koga A, Yamamoto K, Yamamoto M, Moncollin V, Egly JM, Muramatsu M, Tamura T (1997) Molecular cloning of a rat 49-kDa TBP-interacting protein (TIP49) that is highly homologous to the bacterial RuvB. Biochem Biophys Res Commun 235:64–68

    Article  PubMed  CAS  Google Scholar 

  • Kanemaki M, Kurokawa Y, Matsu-ura T, Makino Y, Masani A, Okazaki K, Morishita T, Tamura TA (1999) TIP49b, a new RuvB-like DNA helicase, is included in a complex together with another RuvB-like DNA helicase, TIP49a. J Biol Chem 274:22437–22444

    Article  PubMed  CAS  Google Scholar 

  • Katoh M (2005) WNT/PCP signaling pathway and human cancer (review). Oncol Rep 14:1583–1588

    PubMed  CAS  Google Scholar 

  • Kim JS, Crooks H, Foxworth A, Waldman T (2002) Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitors. Mol Cancer Ther 1:1355–1359

    PubMed  CAS  Google Scholar 

  • Kim S, Xu X, Hecht A, Boyer TG (2006) Mediator is a transducer of Wnt/beta-catenin signaling. J Biol Chem 281:14066–14075

    Article  PubMed  CAS  Google Scholar 

  • Kimelman D, Xu W (2006) Beta-catenin destruction complex: insights and questions from a structural perspective. Oncogene 25:7482–7491

    Article  PubMed  CAS  Google Scholar 

  • Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87:159–170

    Article  PubMed  CAS  Google Scholar 

  • Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, et al. (1991) Identification of FAP locus genes from chromosome 5q21. Science 253:661–665

    Article  PubMed  CAS  Google Scholar 

  • Koehne CH, Dubois RN (2004) COX-2 inhibition and colorectal cancer. Semin Oncol 31:12–21

    Article  PubMed  CAS  Google Scholar 

  • Koesters R, Ridder R, Kopp-Schneider A, Betts D, Adams V, Niggli F, Briner J, von Knebel Doeberitz M (1999) Mutational activation of the beta-catenin proto-oncogene is a common event in the development of Wilms’ tumors. Cancer Res 59:3880–3882

    PubMed  CAS  Google Scholar 

  • Kohn AD, Moon RT (2005) Wnt and calcium signaling: beta-catenin-independent pathways. Cell Calcium 38:439–446

    Article  PubMed  CAS  Google Scholar 

  • Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H (1997) Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC−/− colon carcinoma. Science 275:1784–1787

    Article  PubMed  CAS  Google Scholar 

  • Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ, Clevers H (1998) Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet 19:379–383

    Article  PubMed  CAS  Google Scholar 

  • Koyama T, Tago K, Nakamura T, Ohwada S, Morishita Y, Yokota J, Akiyama T (2002) Mutation and expression of the beta-catenin-interacting protein ICAT in human colorectal tumors. Jpn J Clin Oncol 32:358–362

    Article  PubMed  Google Scholar 

  • Kramps T, Peter O, Brunner E, Nellen D, Froesch B, Chatterjee S, Murone M, Zullig S, Basler K (2002) Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell 109:47–60

    Article  PubMed  CAS  Google Scholar 

  • Kuhnert F, Davis CR, Wang HT, Chu P, Lee M, Yuan J, Nusse R, Kuo CJ (2004) Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc Natl Acad Sci USA 101:266–271

    Article  PubMed  CAS  Google Scholar 

  • Lepourcelet M, Chen YN, France DS, Wang H, Crews P, Petersen F, Bruseo C, Wood AW, Shivdasani RA (2004) Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex. Cancer Cell 5:91–102

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Stevens J, Rote CA, Yost HJ, Hu Y, Neufeld KL, White RL, Matsunami N (2001) Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Mol Cell 7:927–936

    Article  PubMed  CAS  Google Scholar 

  • Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108:837–847

    Article  PubMed  CAS  Google Scholar 

  • Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810

    Article  PubMed  CAS  Google Scholar 

  • Lustig B, Behrens J (2003) The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol 129:199–221

    PubMed  CAS  Google Scholar 

  • Lustig B, Jerchow B, Sachs M, Weiler S, Pietsch T, Karsten U, van de Wetering M, Clevers H, Schlag PM, Birchmeier W, Behrens J (2002) Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol Cell Biol 22:1184–1193

    Article  PubMed  CAS  Google Scholar 

  • Ma H, Nguyen C, Lee KS, Kahn M (2005) Differential roles for the coactivators CBP and p300 on TCF/beta-catenin-mediated survivin gene expression. Oncogene 24:3619–3631

    Article  PubMed  CAS  Google Scholar 

  • Maiti S, Alam R, Amos CI, Huff V (2000) Frequent association of beta-catenin and WT1 mutations in Wilms tumors. Cancer Res 60:6288–6292

    PubMed  CAS  Google Scholar 

  • Malbon CC, Wang HY (2006) Dishevelled: a mobile scaffold catalyzing development. Curr Top Dev Biol 72:153–166

    Article  PubMed  CAS  Google Scholar 

  • Matsuzawa SI, Reed JC (2001) Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Mol Cell 7:915–926

    Article  PubMed  CAS  Google Scholar 

  • Mazieres J, He B, You L, Xu Z, Lee AY, Mikami I, Reguart N, Rosell R, McCormick F, Jablons DM (2004) Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res 64:4717–4720

    Article  PubMed  CAS  Google Scholar 

  • Miller JR (2002) The Wnts. Genome Biol 3: REVIEWS3001

    Google Scholar 

  • Miller JR, Hocking AM, Brown JD, Moon RT (1999) Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways. Oncogene 18:7860–7872

    Article  PubMed  CAS  Google Scholar 

  • Miyagishi M, Fujii R, Hatta M, Yoshida E, Araya N, Nagafuchi A, Ishihara S, Nakajima T, Fukamizu A (2000) Regulation of Lef-mediated transcription and p53-dependent pathway by associating beta-catenin with CBP/p300. J Biol Chem 275:35170–35175

    Article  PubMed  CAS  Google Scholar 

  • Miyaki M, Konishi M, Kikuchi-Yanoshita R, Enomoto M, Igari T, Tanaka K, Muraoka M, Takahashi H, Amada Y, Fukayama M, et al (1994) Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res 54:3011–3020

    PubMed  CAS  Google Scholar 

  • Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, Aoki T, Miki Y, Mori T, Nakamura Y (1992) Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet 1:229–233

    Article  PubMed  CAS  Google Scholar 

  • Miyoshi Y, Iwao K, Nagasawa Y, Aihara T, Sasaki Y, Imaoka S, Murata M, Shimano T, Nakamura Y (1998) Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3. Cancer Res 58:2524–2527

    PubMed  CAS  Google Scholar 

  • Moon RT, Kohn AD, De Ferrari GV, Kaykas A (2004) WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet 5:691–701

    Article  PubMed  CAS  Google Scholar 

  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275:1787–1790

    Article  PubMed  CAS  Google Scholar 

  • Moser AR, Pitot HC, Dove WF (1990) A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247:322–324

    Article  PubMed  CAS  Google Scholar 

  • Mosimann C, Hausmann G, Basler K (2006) Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo. Cell 125:327–341

    Article  PubMed  CAS  Google Scholar 

  • Mulholland DJ, Dedhar S, Coetzee GA, Nelson CC (2005) Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know? Endocr Rev 26:898–915

    Article  PubMed  CAS  Google Scholar 

  • Nath N, Kashfi K, Chen J, Rigas B (2003) Nitric oxide-donating aspirin inhibits beta-catenin/T cell factor (TCF) signaling in SW480 colon cancer cells by disrupting the nuclear beta-catenin-TCF association. Proc Natl Acad Sci USA 100:12584–12589

    Article  PubMed  CAS  Google Scholar 

  • Nelson WJ, Nusse R (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303:1483–1487

    Article  PubMed  CAS  Google Scholar 

  • Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P (1991) Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253:665–669

    Article  PubMed  CAS  Google Scholar 

  • Nusse R (2005) Wnt signaling in disease and in development. Cell Res 15:28–32

    Article  PubMed  CAS  Google Scholar 

  • Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM (1996) Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87:803–809

    Article  PubMed  CAS  Google Scholar 

  • Palacios J, Gamallo C (1998) Mutations in the beta-catenin gene (CTNNB1) in endometrioid ovarian carcinomas. Cancer Res 58:1344–1347

    PubMed  CAS  Google Scholar 

  • Parker DS, Jemison J, Cadigan KM (2002) Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development 129:2565–2576

    PubMed  CAS  Google Scholar 

  • Peifer M, Berg S, Reynolds AB (1994) A repeating amino acid motif shared by proteins with diverse cellular roles. Cell 76:789–791

    Article  PubMed  CAS  Google Scholar 

  • Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, Wakabayashi N, Shen Y, Zimmerman S, Godio L, Rodrigues-Bigas M, Su LK, Sherman J, Kelloff G, Levin B, Steinbach G (2002) A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50:857–860

    Article  PubMed  CAS  Google Scholar 

  • Pinto D, Clevers H (2005) Wnt, stem cells and cancer in the intestine. Biol Cell 97:185–196

    Article  PubMed  CAS  Google Scholar 

  • Pinto D, Gregorieff A, Begthel H, Clevers H (2003) Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev 17:1709–1713

    Article  PubMed  CAS  Google Scholar 

  • Pokutta S, Weis WI (2000) Structure of the dimerization and beta-catenin-binding region of alpha-catenin. Mol Cell 5:533–543

    Article  PubMed  CAS  Google Scholar 

  • Polakis P (2000) Wnt signaling and cancer. Genes Dev 14:1837–1851

    PubMed  CAS  Google Scholar 

  • Polakis P (2002) Casein kinase 1: a Wnt’er of disconnect. Curr Biol 12:R499–R501

    Article  PubMed  CAS  Google Scholar 

  • Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, Thibodeau SN, Vogelstein B, Kinzler KW (1992) APC mutations occur early during colorectal tumorigenesis. Nature 359:235–237

    Article  PubMed  CAS  Google Scholar 

  • Reifenberger J, Knobbe CB, Wolter M, Blaschke B, Schulte KW, Pietsch T, Ruzicka T, Reifenberger G (2002) Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC. Int J Cancer 100:549–556

    Article  PubMed  CAS  Google Scholar 

  • Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–850

    Article  PubMed  CAS  Google Scholar 

  • Roberts CW, Orkin SH (2004) The SWI/SNF complex–chromatin and cancer. Nat Rev Cancer 4:133–142

    PubMed  CAS  Google Scholar 

  • Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, van de Wetering M, Destree O, Clevers H (1998) The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395:608–612

    Article  PubMed  CAS  Google Scholar 

  • Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldschmeding R, Logtenberg T, Clevers H (1999) Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1. Science 285:1923–1926

    Article  PubMed  CAS  Google Scholar 

  • Rottbauer W, Saurin AJ, Lickert H, Shen X, Burns CG, Wo ZG, Kemler R, Kingston R, Wu C, Fishman M (2002) Reptin and pontin antagonistically regulate heart growth in zebrafish embryos. Cell 111:661–672

    Article  PubMed  CAS  Google Scholar 

  • Rozenblatt-Rosen O, Hughes CM, Nannepaga SJ, Shanmugam KS, Copeland TD, Guszczynski T, Resau JH, Meyerson M (2005) The parafibromin tumor suppressor protein is part of a human Paf1 complex. Mol Cell Biol 25:612–620

    Article  PubMed  CAS  Google Scholar 

  • Rubin JS, Barshishat-Kupper M, Feroze-Merzoug F, Xi ZF (2006) Secreted WNT antagonists as tumor suppressors: pro and con. Front Biosci 11:2093–2105

    Article  PubMed  CAS  Google Scholar 

  • Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P (1997) Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 275:1790–1792

    Article  PubMed  CAS  Google Scholar 

  • Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W (2006) Crystal structure of a beta-catenin/BCL9/Tcf4 complex. Mol Cell 24:293–300

    Article  PubMed  CAS  Google Scholar 

  • Sansom OJ, Reed KR, Hayes AJ, Ireland H, Brinkmann H, Newton IP, Batlle E, Simon-Assmann P, Clevers H, Nathke IS, Clarke AR, Winton DJ (2004) Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev 18:1385–1390

    Article  PubMed  CAS  Google Scholar 

  • Schuierer MM, Graf E, Takemaru K, Dietmaier W, Bosserhoff AK (2006) Reduced expression of beta-catenin inhibitor Chibby in colon carcinoma cell lines. World J Gastroenterol 12:1529–1535

    PubMed  CAS  Google Scholar 

  • Segditsas S, Tomlinson I (2006) Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene 25:7531–7537

    Article  PubMed  CAS  Google Scholar 

  • Sekiya T, Nakamura T, Kazuki Y, Oshimura M, Kohu K, Tago K, Ohwada S, Akiyama T (2002) Overexpression of Icat induces G(2) arrest and cell death in tumor cell mutants for adenomatous polyposis coli, beta-catenin, or Axin. Cancer Res 62:3322–3326

    PubMed  CAS  Google Scholar 

  • Shah S, Islam MN, Dakshanamurthy S, Rizvi I, Rao M, Herrell R, Zinser G, Valrance M, Aranda A, Moras D, Norman A, Welsh J, Byers SW (2006) The molecular basis of vitamin D receptor and beta-catenin crossregulation. Mol Cell 21:799–809

    Article  PubMed  CAS  Google Scholar 

  • Sierra J, Yoshida T, Joazeiro CA, Jones KA (2006) The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev 20:586–600

    Article  PubMed  CAS  Google Scholar 

  • Singh AM, Li FQ, Hamazaki T, Kasahara H, Takemaru K, Terada N (2007) Chibby, an antagonist of the Wnt/beta-catenin pathway, facilitates cardiomyocyte differentiation of murine embryonic stem cells. Circulation 115:617–626

    Article  PubMed  CAS  Google Scholar 

  • Sinner D, Rankin S, Lee M, Zorn AM (2004) Sox17 and beta-catenin cooperate to regulate the transcription of endodermal genes. Development 131:3069–3080

    Article  PubMed  CAS  Google Scholar 

  • Solanas G, Miravet S, Casagolda D, Castano J, Raurell I, Corrionero A, de Herreros AG, Dunach M (2004) beta-Catenin and plakoglobin N- and C-tails determine ligand specificity. J Biol Chem 279:49849–49856

    Article  PubMed  CAS  Google Scholar 

  • Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F, Narumiya S, Oshima M, Taketo MM (2001) Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nat Med 7:1048–1051

    Article  PubMed  CAS  Google Scholar 

  • Spiegelman VS, Slaga TJ, Pagano M, Minamoto T, Ronai Z, Fuchs SY (2000) Wnt/beta-catenin signaling induces the expression and activity of betaTrCP ubiquitin ligase receptor. Mol Cell 5:877–882

    Article  PubMed  CAS  Google Scholar 

  • Stadeli R, Hoffmans R, Basler K (2006) Transcription under the control of nuclear Arm/beta-catenin. Curr Biol 16:R378–R385

    Article  PubMed  CAS  Google Scholar 

  • Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, Gould KA, Dove WF (1992) Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256:668–670

    Article  PubMed  CAS  Google Scholar 

  • Su Y, Ishikawa S, Kojima M, Liu B (2003) Eradication of pathogenic beta-catenin by Skp1/Cullin/F box ubiquitination machinery. Proc Natl Acad Sci USA 100:12729–12734

    Article  PubMed  CAS  Google Scholar 

  • Sun Y, Kolligs FT, Hottiger MO, Mosavin R, Fearon ER, Nabel GJ (2000) Regulation of beta – catenin transformation by the p300 transcriptional coactivator. Proc Natl Acad Sci USA 97:12613–12618

    Article  PubMed  CAS  Google Scholar 

  • Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Chen WD, Pretlow TP, Yang B, Akiyama Y, Van Engeland M, Toyota M, Tokino T, Hinoda Y, Imai K, Herman JG, Baylin SB (2004) Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet 36:417–422

    Article  PubMed  CAS  Google Scholar 

  • Tago K, Nakamura T, Nishita M, Hyodo J, Nagai S, Murata Y, Adachi S, Ohwada S, Morishita Y, Shibuya H, Akiyama T (2000) Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein. Genes Dev 14:1741–1749

    PubMed  CAS  Google Scholar 

  • Takemaru K-I (2006) beta-Catenin. AfCS-Nature Molecule Pages (doi:10.1038/mp.a000506.01)

    Google Scholar 

  • Takemaru KI, Moon RT (2000) The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J Cell Biol 149:249–254

    Article  PubMed  CAS  Google Scholar 

  • Takemaru K, Yamaguchi S, Lee YS, Zhang Y, Carthew RW, Moon RT (2003) Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway. Nature 422:905–909

    Article  PubMed  CAS  Google Scholar 

  • Taketo MM (2006) Mouse models of gastrointestinal tumors. Cancer Sci 97:355–361

    Article  PubMed  CAS  Google Scholar 

  • Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426

    Article  PubMed  CAS  Google Scholar 

  • Thompson B, Townsley F, Rosin-Arbesfeld R, Musisi H, Bienz M (2002) A new nuclear component of the Wnt signalling pathway. Nat Cell Biol 4:367–373

    Article  PubMed  CAS  Google Scholar 

  • Thun MJ, Namboodiri MM, Heath CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325:1593–1596

    PubMed  CAS  Google Scholar 

  • Tolwinski NS, Wieschaus E (2004a) A nuclear function for armadillo/beta-catenin. PLoS Biol 2:E95

    Article  PubMed  Google Scholar 

  • Tolwinski NS, Wieschaus E (2004b) Rethinking WNT signaling. Trends Genet 20:177–181

    Article  PubMed  CAS  Google Scholar 

  • Torrance CJ, Jackson PE, Montgomery E, Kinzler KW, Vogelstein B, Wissner A, Nunes M, Frost P, Discafani CM (2000) Combinatorial chemoprevention of intestinal neoplasia. Nat Med 6:1024–1028

    Article  PubMed  CAS  Google Scholar 

  • Townsley FM, Cliffe A, Bienz M (2004) Pygopus and Legless target Armadillo/beta-catenin to the nucleus to enable its transcriptional co-activator function. Nat Cell Biol 6:626–633

    Article  PubMed  CAS  Google Scholar 

  • Truica CI, Byers S, Gelmann EP (2000) Beta-catenin affects androgen receptor transcriptional activity and ligand specificity. Cancer Res 60:4709–4713

    PubMed  CAS  Google Scholar 

  • Tutter AV, Fryer CJ, Jones KA (2001) Chromatin-specific regulation of LEF-1-beta-catenin transcription activation and inhibition in vitro. Genes Dev 15:3342–3354

    Article  PubMed  CAS  Google Scholar 

  • Uusitalo M, Heikkila M, Vainio S (1999) Molecular genetic studies of Wnt signaling in the mouse. Exp Cell Res 253:336–348

    Article  PubMed  CAS  Google Scholar 

  • van Amerongen R, Berns A (2006) Knockout mouse models to study Wnt signal transduction. Trends Genet 22:678–689

    Article  PubMed  CAS  Google Scholar 

  • van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J, Ypma A, Hursh D, Jones T, Bejsovec A, Peifer M, Mortin M, Clevers H (1997) Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88:789–799

    Article  PubMed  Google Scholar 

  • van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, van der Horn K, Batlle E, Coudreuse D, Haramis AP, Tjon-Pon-Fong M, Moerer P, van den Born M, Soete G, Pals S, Eilers M, Medema R, Clevers H (2002) The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111:241–250

    Article  PubMed  Google Scholar 

  • van de Wetering M, Oving I, Muncan V, Pon Fong MT, Brantjes H, van Leenen D, Holstege FC, Brummelkamp TR, Agami R, Clevers H (2003) Specific inhibition of gene expression using a stably integrated, inducible small-interfering-RNA vector. EMBO Rep 4:609–615

    Article  PubMed  CAS  Google Scholar 

  • van Es JH, Jay P, Gregorieff A, van Gijn ME, Jonkheer S, Hatzis P, Thiele A, van den Born M, Begthel H, Brabletz T, Taketo MM, Clevers H (2005) Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat Cell Biol 7:381–386

    Article  PubMed  CAS  Google Scholar 

  • Veeman MT, Axelrod JD, Moon RT (2003) A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell 5:367–377

    Article  PubMed  CAS  Google Scholar 

  • Verma UN, Surabhi RM, Schmaltieg A, Becerra C, Gaynor RB (2003) Small interfering RNAs directed against beta-catenin inhibit the in vitro and in vivo growth of colon cancer cells. Clin Cancer Res 9:1291–1300

    PubMed  CAS  Google Scholar 

  • Vleminckx K, Kemler R, Hecht A (1999) The C-terminal transactivation domain of beta-catenin is necessary and sufficient for signaling by the LEF-1/beta-catenin complex in Xenopus laevis. Mech Dev 81:65–74

    Article  PubMed  CAS  Google Scholar 

  • Waltzer L, Bienz M (1998) Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling. Nature 395:521–525

    Article  PubMed  CAS  Google Scholar 

  • Wang HY, Liu T, Malbon CC (2006) Structure-function analysis of Frizzleds. Cell Signal 18:934–941

    Article  PubMed  CAS  Google Scholar 

  • Wang PF, Tan MH, Zhang C, Morreau H, Teh BT (2005) HRPT2, a tumor suppressor gene for hyperparathyroidism-jaw tumor syndrome. Horm Metab Res 37:380–383

    Article  PubMed  CAS  Google Scholar 

  • Willert K, Jones KA (2006) Wnt signaling: is the party in the nucleus? Genes Dev 20:1394–1404

    Article  PubMed  CAS  Google Scholar 

  • Williams CS, Smalley W, DuBois RN (1997) Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Invest 100:1325–1329

    Article  PubMed  CAS  Google Scholar 

  • Willis TG, Zalcberg IR, Coignet LJ, Wlodarska I, Stul M, Jadayel DM, Bastard C, Treleaven JG, Catovsky D, Silva ML, Dyer MJ (1998) Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21. Blood 91:1873–1881

    PubMed  CAS  Google Scholar 

  • Wodarz A, Nusse R (1998) Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol 14:59–88

    Article  PubMed  CAS  Google Scholar 

  • Xing Y, Clements WK, Kimelman D, Xu W (2003) Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex. Genes Dev 17:2753–2764

    Article  PubMed  CAS  Google Scholar 

  • Xing Y, Clements WK, Le Trong I, Hinds TR, Stenkamp R, Kimelman D, Xu W (2004) Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function. Mol Cell 15:523–533

    Article  PubMed  CAS  Google Scholar 

  • Yang K, Fan K, Kurihara N, Shinozaki H, Rigas B, Augenlicht L, Kopelovich L, Edelmann W, Kucherlapati R, Lipkin M (2003) Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations. Carcinogenesis 24:605–611

    Article  PubMed  CAS  Google Scholar 

  • Yang CK, Kim JH, Li H, Stallcup MR (2006) Differential use of functional domains by coiled-coil coactivator in its synergistic coactivator function with beta-catenin or GRIP1. J Biol Chem 281:3389–3397

    Article  PubMed  CAS  Google Scholar 

  • Yart A, Gstaiger M, Wirbelauer C, Pecnik M, Anastasiou D, Hess D, Krek W (2005) The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol 25:5052–5060

    Article  PubMed  CAS  Google Scholar 

  • You L, He B, Xu Z, Uematsu K, Mazieres J, Fujii N, Mikami I, Reguart N, McIntosh JK, Kashani-Sabet M, McCormick F, Jablons DM (2004) An anti-Wnt-2 monoclonal antibody induces apoptosis in malignant melanoma cells and inhibits tumor growth. Cancer Res 64:5385–5389

    Article  PubMed  CAS  Google Scholar 

  • Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J, He X (2005) A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 438:873–877

    Article  PubMed  CAS  Google Scholar 

  • Zirn B, Wittmann S, Graf N, Gessler M (2005) Chibby, a novel antagonist of the Wnt pathway, is not involved in Wilms tumor development. Cancer Lett 220:115–120

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY, 11794, USA

    K. -I. Takemaru, M. Ohmitsu & F. -Q. Li

Authors
  1. K. -I. Takemaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Ohmitsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. -Q. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Leibniz-Institut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany

    Enno Klussmann

  2. The Vollum Institute, Oregon Health & Science University, Medical Research Bldg, Rm 322D 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA

    John Scott Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Takemaru, K.I., Ohmitsu, M., Li, F.Q. (2008). An Oncogenic Hub: β-Catenin as a Molecular Target for Cancer Therapeutics. In: Klussmann, E., Scott, J. (eds) Protein-Protein Interactions as New Drug Targets. Handbook of Experimental Pharmacology, vol 186. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-72843-6_11

Download citation

Publish with us

Policies and ethics

Search

Navigation