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Signalling Pathways of β-Catenin/JNK in Carcinogenesis

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Abstract

Tight control of signalling/transcriptional activity ensures that the correct balance between gene expression changes regulating the cell cycle, DNA repair, developmental potential and fate determination is maintained by different cells. Activation of the Wnt signalling pathway stimulates growth and mediates developmental and carcinogenic signalling between cells. In fact, a Wnt pathway mutation, such as loss of the adenomatous polyposis coli gene, is sufficient to give rise to a tumor that grows without limit. This suggests that the mutation, through ectopically activating the Wnt pathway, may also switch on associated pathways; Notch, Eph/ephrin, bone morphogenetic protein, Hedgehog and mitogen-activated protein kinase, as observed in the Apc Min/+ mouse model of intestinal carcinogenesis. Wnt signalling can also activate non-canonical, β-catenin-independent pathways, including activation of the c-Jun N-terminal kinase (JNK). JNK activation, which can occur via many types of cellular stress or extracellular signals, plays an essential role in organogenesis during mouse development by regulating cell proliferation, survival and apoptosis. JNK activation is also involved in messenger RNA stabilization, cell migration, cytoskeleton integrity and carcinogenesis. However, the links between the β-catenin and JNK pathways are poorly understood, and the identities of the downstream targets/effectors of Wnt/JNK remain largely unknown. Moreover, little is known about the effect of phosphorylation by JNK on the functions of the possible common targets between these two pathways. This chapter discusses the relations between the β-catenin and JNK pathways and their identifies component genes involved in carcinogenesis.

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Abbreviations

AP1:

Activator protein 1

APC:

Adenomatous polyposis coli

GSK3β:

Glycogen synthase kinase 3β

HMG:

High mobility group

JNK:

c-Jun N-terminal kinase

LEF:

Lymphoid enhancer factor

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloproteinase

STAT:

Signal transducer and activator of transcription

TCF:

T cell factor

References

  • Aguilera C, Nakagawa K, Sancho R, Chakraborty A, Hendrich B, Behrens A (2011) c-Jun N-terminal phosphorylation antagonises recruitment of the Mbd3/NuRD repressor complex. Nature 469:231–235

    Google Scholar 

  • Ahokas K, Skoog T, Suomela S, Jeskanen L, Impola U, Isaka K, Saarialho-Kere U (2005) Matrilysin-2 (matrix metalloproteinase-26) is upregulated in keratinocytes during wound repair and early skin carcinogenesis. J Invest Dermatol 124:849–856

    PubMed  CAS  Google Scholar 

  • Babaei-Jadidi R, Li N, Saadeddin A, Spencer-Dene B, Jandke A, Muhammad B, Ibrahim EE, Muraleedharan R, Abuzinadah M, Davis H, Lewis A, Watson S, Behrens A, Tomlinson I, Nateri AS (2011) FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. J Exp Med 208:295–312

    Google Scholar 

  • Behrens A, Jochum W, Sibilia M, Wagner EF (2000) Oncogenic transformation by ras and fos is mediated by c-Jun N-terminal phosphorylation. Oncogene 19:2657–2663

    PubMed  CAS  Google Scholar 

  • Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W (1996) Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382:638–642

    PubMed  CAS  Google Scholar 

  • Behrens J, Lustig B (2004) The Wnt connection to tumorigenesis. Int J Dev Biol 48:477–487

    PubMed  CAS  Google Scholar 

  • Bhanot P, Brink M, Samos CH, Hsieh J-C, Wang Y, Macke JP, Andrew D, Nathans J, Nusse R (1996) A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382:225–230

    PubMed  CAS  Google Scholar 

  • Bilic J, Huang YL, Davidson G, Zimmermann T, Cruciat CM, Bienz M, Niehrs C (2007) Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science 316:1619–1622

    PubMed  CAS  Google Scholar 

  • Bogoyevitch MA, Kobe B (2006) Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases. Microbiol Mol Biol Rev 70:1061–1095

    PubMed  CAS  Google Scholar 

  • Brannon M, Gomperts M, Sumoy L, Moon RT, Kimelman D (1997) A β-catenin/XTcf-3 complex binds to thesiamois promoter to regulate dorsal axis specification in Xenopus. Gene Dev 11:2359–2370

    PubMed  CAS  Google Scholar 

  • Brantjes H, Roose J, van de Wetering M, Clevers H (2001) All Tcf HMG box transcription factors interact with Groucho-related co-repressors. Nucleic Acids Res 29:1410–1419

    PubMed  CAS  Google Scholar 

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

    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

    PubMed  CAS  Google Scholar 

  • Chang Q, Chen J, Beezhold KJ, Castranova V, Shi X, Chen F (2009a) JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma. Mol Cancer 8(64):1−14

    Google Scholar 

  • Chang Q, Zhang Y, Beezhold KJ, Bhatia D, Zhao H, Chen J, Castranova V, Shi X, Chen F (2009b) Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer. J Hepatol 50:323–333

    PubMed  CAS  Google Scholar 

  • Chen F (2012) JNK-induced apoptosis, compensatory growth, and cancer stem cells. Cancer Res 72:379–386

    PubMed  CAS  Google Scholar 

  • Chen N, Nomura M, She Q-B, Ma W-Y, Bode AM, Wang L, Flavell RA, Dong Z (2001) Suppression of skin tumorigenesis in c-Jun NH2-terminal kinase-2-deficient mice. Cancer Res 61:3908–3912

    PubMed  CAS  Google Scholar 

  • Choi HS, Bode AM, Shim J-H, Lee S-Y, Dong Z (2009) c-Jun N-terminal kinase 1 phosphorylates Myt1 to prevent UVA-induced skin cancer. Mol Cell Biol 29:2168–2180

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Courey AJ, Jia S (2001) Transcriptional repression: the long and the short of it. Gene 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

    PubMed  CAS  Google Scholar 

  • Crawford HC, Fingleton B, Gustavson MD, Kurpios N, Wagenaar RA, Hassell JA, Matrisian LM (2001) The PEA3 subfamily of Ets transcription factors synergizes with beta-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Mol Cell Biol 21:1370–1383

    PubMed  CAS  Google Scholar 

  • Dérijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ (1994) JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76:1025–1037

    PubMed  Google Scholar 

  • Durbin AD, Hannigan GE, Malkin D (2009a) Oncogenic ILK, tumor suppression and all that JNK. Cell Cycle 8:4060–4066

    PubMed  CAS  Google Scholar 

  • Durbin AD, Somers GR, Forrester M, Pienkowska M, Hannigan GE, Malkin D (2009b) JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma. J Clin Investig 119:1558–1570

    PubMed  CAS  Google Scholar 

  • Eferl R, Wagner EF (2003) AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3:859–868

    PubMed  CAS  Google Scholar 

  • El-Tanani M, Platt-Higgins A, Rudland PS, Campbell FC (2004) Ets gene PEA3 cooperates with beta-catenin-Lef-1 and c-Jun in regulation of osteopontin transcription. J Biol Chem 279:20794–20806

    PubMed  CAS  Google Scholar 

  • Engelberg D (2004) Stress-activated protein kinases—tumor suppressors or tumor initiators? Semin Cancer Biol 14:271–282

    PubMed  CAS  Google Scholar 

  • Gan XQ, Wang JY, Xi Y, Wu ZL, Li YP, Li L (2008) Nuclear Dvl, c-Jun, beta-catenin, and TCF form a complex leading to stabilization of beta-catenin-TCF interaction. J Cell Biol 180:1087–1100

    PubMed  CAS  Google Scholar 

  • Gerdes MJ, Myakishev M, Frost NA, Rishi V, Moitra J, Acharya A, Levy MR, Park SW, Glick A, Yuspa SH, Vinson C (2006) Activator protein-1 activity regulates epithelial tumor cell identity. Cancer Res 66:7578–7588

    PubMed  CAS  Google Scholar 

  • Giese K, Cox J, Grosschedl R (1992) The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69:185–195

    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 

  • González-García A, Pritchard CA, Paterson HF, Mavria G, Stamp G, Marshall CJ (2005) RalGDS is required for tumor formation in a model of skin carcinogenesis. Cancer Cell 7:219–226

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Derijard B, Davis RJ (1996) Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 15:2760–2770

    PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    PubMed  CAS  Google Scholar 

  • Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P (1998) Downregulation of β-catenin by human axin and its association with the APC tumor suppressor, β-catenin and GSK3β. Curr Biol 8:573–581

    Google Scholar 

  • Hayakawa J, Mittal S, Wang Y, Korkmaz KS, Adamson E, English C, Ohmichi M, McClelland M, Mercola D (2004) Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress. Mol Cell 16:521–535

    PubMed  CAS  Google Scholar 

  • Hess P, Pihan G, Sawyers CL, Flavell RA, Davis RJ (2002) Survival signaling mediated by c-Jun NH2-terminal kinase in transformed B lymphoblasts. Nat Genet 32:201–205

    PubMed  CAS  Google Scholar 

  • Hideshima T, Hayashi T, Chauhan D, Akiyama M, Richardson P, Anderson K (2003) Biologic sequelae of c-Jun NH2-terminal kinase (JNK) activation in multiple myeloma cell lines. Oncogene 22:8797–8801

    Google Scholar 

  • Hinck L, Nelson WJ, Papkoff J (1994) Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin. J Cell Biol 124:729–741

    PubMed  CAS  Google Scholar 

  • Hu D, Fang W, Han A, Gallagher L, Davis RJ, Xiong B, Yang W (2008) c-Jun N-terminal kinase 1 interacts with and negatively regulates Wnt/β-catenin signaling through GSK3β pathway. Carcinogenesis 29:2317–2324

    PubMed  CAS  Google Scholar 

  • Huang H, He X (2008) Wnt/β-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 20:119–125

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann BG, Kemler R (1996) Nuclear localization of β-catenin by interaction with transcription factor LEF-1. Mech Dev 59:3–10

    PubMed  CAS  Google Scholar 

  • Hui L, Zatloukal K, Scheuch H, Stepniak E, Wagner EF (2008) Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. J Clin Investig 118:3943–3953

    PubMed  CAS  Google Scholar 

  • Hwang SG, Yu SS, Lee SW, Chun JS (2005) Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway. FEBS Lett 579:4837–4842

    PubMed  CAS  Google Scholar 

  • Igaki T, Pagliarini RA, Xu T (2006) Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr Biol 16:1139–1146

    PubMed  CAS  Google Scholar 

  • Jochum W, Passegue E, Wagner EF (2001) AP-1 in mouse development and tumorigenesis. Oncogene 20:2401–2412

    PubMed  CAS  Google Scholar 

  • Karin M, Gallagher E (2005) From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance. IUBMB Life 57:283–295

    PubMed  CAS  Google Scholar 

  • Kennedy NJ, Sluss HK, Jones SN, Bar-Sagi D, Flavell RA, Davis RJ (2003) Suppression of Ras-stimulated transformation by the JNK signal transduction pathway. Gene Dev 17:629–637

    PubMed  CAS  Google Scholar 

  • Kitagawa M, Hatakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, Nakamichi I, Kikuchi A, Nakayama K-I, Nakayama K (1999) An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of [beta]-catenin. EMBO J 18:2401–2410

    Google Scholar 

  • Klaus A, Birchmeier W (2008) Wnt signalling and its impact on development and cancer. Nat Rev Cancer 8:387–398

    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 β-Catenin-Tcf complex in APC−/− colon carcinoma. Science 275:1784–1787

    PubMed  CAS  Google Scholar 

  • Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869

    PubMed  CAS  Google Scholar 

  • Le Floch N, Rivat C, De Wever O, Bruyneel E, Mareel M, Dale T, Gespach C (2005) The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3beta and c-Jun/AP-1 signaling. FASEB J 19(1):144–146

    PubMed  Google Scholar 

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

    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

    PubMed  CAS  Google Scholar 

  • Lopez-Bergami P, Huang C, Goydos JS, Yip D, Bar-Eli M, Herlyn M, Smalley KSM, Mahale A, Eroshkin A, Aaronson S, Ronai Ze (2007) Rewired ERK-JNK signaling pathways in melanoma. Cancer Cell 11:447–460

    Google Scholar 

  • Love JJ, Li X, Case DA, Giese K, Crosschedl R, Wright PE (1995) Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature 376:791–795

    PubMed  CAS  Google Scholar 

  • Maeda S, Kamata H, Luo J-L, Leffert H, Karin M (2005) IKKβ couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121:977–990

    PubMed  CAS  Google Scholar 

  • Mamay CL, Mingo-Sion AM, Wolf DM, Molina MD, Van Den Berg CL (2003) An inhibitory function for JNK in the regulation of IGF-I signaling in breast cancer. Oncogene 22:602–614

    Google Scholar 

  • Manning AM, Davis RJ (2003) Targeting JNK for therapeutic benefit: from junk to gold? Nat Rev Drug Discov 2:554–565

    PubMed  CAS  Google Scholar 

  • Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C (2001) LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature 411:321–325

    PubMed  CAS  Google Scholar 

  • Marchenko ND, Marchenko GN, Weinreb RN, Lindsey JD, Kyshtoobayeva A, Crawford HC, Strongin AY (2004) Beta-catenin regulates the gene of MMP-26, a novel metalloproteinase expressed both in carcinomas and normal epithelial cells. Int J Biochem Cell Biol 36:942–956

    PubMed  CAS  Google Scholar 

  • McDonnell S, Navre M, Coffey RJ Jr, Matrisian LM (1991) Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas. Mol Carcinog 4:527–533

    PubMed  CAS  Google Scholar 

  • McNeill H, Woodgett JR (2010) When pathways collide: collaboration and connivance among signalling proteins in development. Nat Rev Mol Cell Biol 11:404–413

    PubMed  CAS  Google Scholar 

  • Mialon A, Sankinen M, Söderström H, Junttila TT, Holmström T, Koivusalo R, Papageorgiou AC, Johnson RS, Hietanen S, Elenius K, Westermarck J (2005) DNA topoisomerase I is a cofactor for c-Jun in the regulation of epidermal growth factor receptor expression and cancer cell proliferation. Mol Cell Biol 25:5040–5051

    PubMed  CAS  Google Scholar 

  • Minden A, Lin A, Smeal T, Dérijard B, Cobb M, Davis R, Karin M (1994) c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases. Mol Cell Biol 14:6683–6688

    PubMed  CAS  Google Scholar 

  • Mingo-Sion AM, Marietta PM, Koller E, Wolf DM, Van Den Berg CL (2004) Inhibition of JNK reduces G2//M transit independent of p53, leading to endoreduplication, decreased proliferation, and apoptosis in breast cancer cells. Oncogene 23:596–604

    Google Scholar 

  • Monno S, Newman MV, Cook M, Lowe WL (2000) Insulin-like growth factor I activates c-Jun N-terminal kinase in MCF-7 breast cancer cells. Endocrinology 141:544–550

    PubMed  CAS  Google Scholar 

  • Morata G, Shlevkov E, Pérez-Garijo A (2011) Mitogenic signaling from apoptotic cells in Drosophila. Dev Growth Differ 53:168–176

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Munemitsu S, Albert I, Souza B, Rubinfeld B, Polakis P (1995) Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein. Proc Natl Acad Sci USA 92:3046–3050

    PubMed  CAS  Google Scholar 

  • Munoz J, Stange DE, Schepers AG, van de Wetering M, Koo BK, Itzkovitz S, Volckmann R, Kung KS, Koster J, Radulescu S, Myant K, Versteeg R, Sansom OJ, van Es JH, Barker N, van Oudenaarden A, Mohammed S, Heck AJ, Clevers H (2012) The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent ‘ + 4’ cell markers. EMBO J 31:3079–3091

    Google Scholar 

  • Nateri AS, Spencer-Dene B, Behrens A (2005) Interaction of phosphorylated c-Jun with TCF4 regulates intestinal cancer development. Nature 437:281–285

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Patani N, Jouhra F, Jiang W, Mokbel K (2008) Osteopontin expression profiles predict pathological and clinical outcome in breast cancer. Anticancer Res 28:4105–4110

    PubMed  CAS  Google Scholar 

  • Paul P (2007) The many ways of Wnt in cancer. Curr Opin Genet Dev 17:45–51

    Google Scholar 

  • Peifer M, Polakis P (2000) Wnt signaling in oncogenesis and embryogenesis—a look outside the nucleus. Science 287:1606–1609

    PubMed  CAS  Google Scholar 

  • Phelps RA, Chidester S, Dehghanizadeh S, Phelps J, Sandoval IT, Rai K, Broadbent T, Sarkar S, Burt RW, Jones DA (2009) A two-step model for colon adenoma initiation and progression caused by APC loss. Cell 137:623–634

    PubMed  CAS  Google Scholar 

  • Pilka R, Norata GD, Domanski H, Andersson C, Hansson S, Eriksson P, Casslen B (2004) Matrix metalloproteinase-26 (matrilysin-2) expression is high in endometrial hyperplasia and decreases with loss of histological differentiation in endometrial cancer. Gynecol Oncol 94:661–670

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Potapova O, Gorospe M, Bost F, Dean NM, Gaarde WA, Mercola D, Holbrook NJ (2000) c-Jun N-terminal kinase is essential for growth of human T98G glioblastoma cells. J Biol Chem 275:24767–24775

    PubMed  CAS  Google Scholar 

  • Potapova O, Basu S, Mercola D, Holbrook NJ (2001) Protective role for c-Jun in the cellular response to DNA damage. J Biol Chem 276:28546–28553

    PubMed  CAS  Google Scholar 

  • Potapova O, Haghighi A, Bost F, Liu C, Birrer MJ, Gjerset R, Mercola D (1997) The Jun kinase/stress-activated protein kinase pathway functions to regulate DNA repair and inhibition of the pathway sensitizes tumor cells to cisplatin. J Biol Chem 272:14041–14044

    PubMed  CAS  Google Scholar 

  • Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR (1991) Phosphorylation of c-jun mediated by MAP kinases. Nature 353:670–674

    PubMed  CAS  Google Scholar 

  • Raftopoulou M (2005) Tumorigenesis: TCF4 feeds c-Jun. Nat Cell Biol 7:932

    PubMed  CAS  Google Scholar 

  • Rivat C, Le Floch N, Sabbah M, Teyrol I, Redeuilh G, Bruyneel E, Mareel M, Matrisian LM, Crawford HC, Gespach C, Attoub S (2003) Synergistic cooperation between the AP-1 and LEF-1 transcription factors in activation of the matrilysin promoter by the src oncogene: implications in cellular invasion. FASEB J 17:1721–1723

    PubMed  CAS  Google Scholar 

  • Roger JD (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252

    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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Ryoo HD, Gorenc T, Steller H (2004) Apoptotic cells can induce compensatory cell proliferation through the JNK and the wingless signaling pathways. Dev Cell 7:491–501

    PubMed  CAS  Google Scholar 

  • Saadeddin A, Babaei-Jadidi R, Spencer-Dene B, Nateri AS (2009) The links between transcription, β-catenin/JNK signaling, and carcinogenesis. Mol Cancer Res 7:1189–1196

    PubMed  CAS  Google Scholar 

  • Sabapathy K, Hochedlinger K, Nam SY, Bauer A, Karin M, Wagner EF (2004) Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation. Mol Cell 15:713–725

    PubMed  CAS  Google Scholar 

  • Sabapathy K, Wagner EF (2004) JNK2: A negative regulator of cellular proliferation. Cell Cycle 3:1520–1523

    PubMed  CAS  Google Scholar 

  • Sabates-Bellver J, Van der Flier LG, de Palo M, Cattaneo E, Maake C, Rehrauer H, Laczko E, Kurowski MA, Bujnicki JM, Menigatti M, Luz J, Ranalli TV, Gomes V, Pastorelli A, Faggiani R, Anti M, Jiricny J, Clevers H, Marra G (2007) Transcriptome profile of human colorectal adenomas. Mol Cancer Res 5:1263–1275

    PubMed  CAS  Google Scholar 

  • Sakurai T, Maeda S, Chang L, Karin M (2006) Loss of hepatic NF-κB activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc Natl Acad Sci USA 103:10544–10551

    PubMed  CAS  Google Scholar 

  • Sancho R, Nateri AS, de Vinuesa AG, Aguilera C, Nye E, Spencer-Dene B, Behrens A (2009) JNK signalling modulates intestinal homeostasis and tumorigenesis in mice. EMBO J 28:1843–1854

    PubMed  CAS  Google Scholar 

  • Seidensticker MJ, Behrens J (2000) Biochemical interactions in the wnt pathway. Biochim Biophys Acta 1495:168–182

    PubMed  CAS  Google Scholar 

  • She Q-B, Chen N, Bode AM, Flavell RA, Dong Z (2002) Deficiency of c-Jun-NH2-terminal kinase-1 in mice enhances skin tumor development by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 62:1343–1348

    PubMed  CAS  Google Scholar 

  • Shibata W, Maeda S, Hikiba Y, Yanai A, Sakamoto K, Nakagawa H, Ogura K, Karin M, Omata M (2008) c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice. Cancer Res 68:5031–5039

    PubMed  CAS  Google Scholar 

  • Smeal T, Binetruy B, Mercola DA, Birrer M, Karin M (1991) Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73. Nature 354:494–496

    PubMed  CAS  Google Scholar 

  • Smeal T, Binetruy B, Mercola D, Grover-Bardwick A, Heidecker G, Rapp UR, Karin M (1992) Oncoprotein-mediated signalling cascade stimulates c-Jun activity by phosphorylation of serines 63 and 73. Mol Cell Biol 12:3507–3513

    PubMed  CAS  Google Scholar 

  • Srinivas H, Juroske DM, Kalyankrishna S, Cody DD, Price RE, Xu X-C, Narayanan R, Weigel NL, Kurie JM (2005) c-Jun N-terminal kinase contributes to aberrant retinoid signaling in lung cancer cells by phosphorylating and inducing proteasomal degradation of retinoic acid receptor α. Mol Cell Biol 25:1054–1069

    PubMed  CAS  Google Scholar 

  • Takahashi H, Ogata H, Nishigaki R, Broide DH, Karin M (2010) Tobacco smoke promotes lung tumorigenesis by triggering IKK beta- and JNK1-dependent inflammation. Cancer Cell 17:89–97

    PubMed  CAS  Google Scholar 

  • Takeda K, Kinoshita I, Shimizu Y, Ohba Y, Itoh T, Matsuno Y, Shichinohe T, Dosaka-Akita H (2008) Clinicopathological significance of expression of p-c-Jun, TCF4 and beta-catenin in colorectal tumors. BMC Cancer 8:328

    PubMed  Google Scholar 

  • Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet J-P, He X (2000) LDL-receptor-related proteins in Wnt signal transduction. Nature 407:530–535

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Tong C, Yin Z, Song Z, Dockendorff A, Huang C, Mariadason J, Flavell RA, Davis RJ, Augenlicht LH, Yang W (2007) c-Jun NH2-terminal kinase 1 plays a critical role in intestinal homeostasis and tumor suppression. Am J Pathol 171:297–303

    PubMed  CAS  Google Scholar 

  • Toualbi K, Guller MC, Mauriz JL, Labalette C, Buendia MA, Mauviel A, Bernuau D (2007) Physical and functional cooperation between AP-1 and beta-catenin for the regulation of TCF-dependent genes. Oncogene 26:3492–3502

    PubMed  CAS  Google Scholar 

  • Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, Bar-Sagi D, Jones SN, Flavell RA, Davis RJ (2000) Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 288:870–874

    PubMed  CAS  Google Scholar 

  • Van der Flier LG, Sabates-Bellver J, Oving I, Haegebarth A, De Palo M, Anti M, Van Gijn ME, Suijkerbuijk S, Van de Wetering M, Marra G, Clevers H (2007) The intestinal Wnt/TCF signature. Gastroenterology 132:628–632

    PubMed  Google Scholar 

  • Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789–799

    PubMed  CAS  Google Scholar 

  • Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9:537–549

    PubMed  CAS  Google Scholar 

  • Wang T-H, Wang H-S, Ichijo H, Giannakakou P, Foster JS, Fojo T, Wimalasena J (1998) Microtubule-interfering agents activate c-Jun N-terminal kinase/stress-activated protein kinase through both Ras and apoptosis signal-regulating kinase pathways. J Biol Chem 273:4928–4936

    PubMed  CAS  Google Scholar 

  • Weber GF (2001) The metastasis gene osteopontin: a candidate target for cancer therapy. Biochim Biophys Acta 1552:61–85

    PubMed  CAS  Google Scholar 

  • Wehrli M, Dougan ST, Caldwell K, O’Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S (2000) Arrow encodes an LDL-receptor-related protein essential for wingless signalling. Nature 407:527–530

    PubMed  CAS  Google Scholar 

  • Weston CR, Davis RJ (2002) The JNK signal transduction pathway. Curr Opin Genet Dev 12:14–21

    PubMed  CAS  Google Scholar 

  • Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW (1999) The SCFβ-TRCP–ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IκBα and β-catenin and stimulates IκBα ubiquitination in vitro. Gene Dev 13:270–283

    PubMed  CAS  Google Scholar 

  • Wisdom R, Johnson RS, Moore C (1999) c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. EMBO J 18:188–197

    PubMed  CAS  Google Scholar 

  • Wu M, Pastor-Pareja JC, Xu T (2010) Interaction between RasV12 and scribbled clones induces tumor growth and invasion. Nature 463:545–548

    PubMed  CAS  Google Scholar 

  • Wulf GM, Ryo A, Wulf GG, Lee SW, Niu T, Petkova V, Lu KP (2001) Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. EMBO J 20:3459–3472

    PubMed  CAS  Google Scholar 

  • Yamagata H, Matsuzaki K, Mori S, Yoshida K, Tahashi Y, Furukawa F, Sekimoto G, Watanabe T, Uemura Y, Sakaida N, Yoshioka K, Kamiyama Y, Seki T, Okazaki K (2005) Acceleration of Smad2 and Smad3 phosphorylation via c-Jun NH2-terminal kinase during human colorectal carcinogenesis. Cancer Res 65:157–165

    PubMed  CAS  Google Scholar 

  • Yochum GS, Cleland R, Goodman RH (2008) A genome-wide screen for beta-catenin binding sites identifies a downstream enhancer element that controls c-Myc gene expression. Mol Cell Biol 28:7368–7379

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank our colleagues in the laboratory for reading the manuscript and providing comments. The Cancer Genetics and Stem Cell Group studies are supported by research grants from the Medical Research Council and Cancer Research UK.

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  1. Cancer Genetics and Stem Cell Group, Division of Pre-Clinical Oncology, Nottingham Digestive Diseases Centre Biomedical Research Unit, School of Clinical Sciences, University of Nottingham, Nottingham, NG7 2UH, UK

    Eliana Kalakouti, Roya Babaei-Jadidi & Abdolrahman S. Nateri

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  1. Eliana Kalakouti
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  2. Roya Babaei-Jadidi
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  3. Abdolrahman S. Nateri
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Correspondence to Abdolrahman S. Nateri .

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  1. Instituto de Ciências Biológicas, Departamento de Bioquímica, Universidade Federal de Minas Gerais, Belo Horizonte, São Paulo, Brazil

    Rodrigo R. Resende

  2. Depto. Bioquímica, Universidade de São Paulo Inst. Química, São Paulo, São Paulo, Brazil

    Henning Ulrich

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Kalakouti, E., Babaei-Jadidi, R., Nateri, A.S. (2013). Signalling Pathways of β-Catenin/JNK in Carcinogenesis. In: Resende, R., Ulrich, H. (eds) Trends in Stem Cell Proliferation and Cancer Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6211-4_11

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