The regulation of β-catenin activity and function in cancer: therapeutic opportunities

Nusse, 1984, Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding domain intact, Cell, 39, 233, 10.1016/0092-8674(84)90209-5

Birchmeier, 1996, Functional interaction of beta-catenin with the transcription factor LEF-1, Nature, 382, 638, 10.1038/382638a0

Casey, 1994, Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for wingless signal and zeste-white 3 kinase, Dev Biol, 166, 543, 10.1006/dbio.1994.1336

Polakis, 1996, Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly, Science, 272, 1023, 10.1126/science.272.5264.1023

Moon, 1996, The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3, Genes Dev, 10, 1443, 10.1101/gad.10.12.1443

Goss, 2010, Wnt/beta-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome, Am J Pathol, 176, 2911, 10.2353/ajpath.2010.091125

Evert, 2014, Activation of beta-catenin and Yap1 in human hepatoblastoma and induction of hepatocarcinogenesis in mice, Gastroenterology, 147, 690, 10.1053/j.gastro.2014.05.004

Asakura, 2000, Nuclear translocation of beta-catenin in colorectal cancer, Br J Cancer, 82, 1689

Bosenberg, 2011, β-Catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas, Cancer Cell, 20, 741, 10.1016/j.ccr.2011.10.030

Bigas, 2016, β-Catenin is required for T-cell leukemia initiation and MYC transcription downstream of Notch1, Leukemia, 30, 2002, 10.1038/leu.2016.106

Williams, 2011, Wnt/beta-catenin Signaling in Normal and Cancer Stem Cells, Cancers (Basel), 3, 2050, 10.3390/cancers3022050

Manicassamy, 2015, β-Catenin promotes regulatory T-cell responses in tumors by inducing vitamin A metabolism in dendritic cells, Cancer Res, 75, 656, 10.1158/0008-5472.CAN-14-2377

Silver, 2005, Exon 3 beta-catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome, Gut, 54, 264, 10.1136/gut.2004.048132

Kinzler, 1997, Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC, Science, 275, 1787, 10.1126/science.275.5307.1787

Dawson, 2012, Dysregulation of Wnt/beta-catenin signaling in gastrointestinal cancers, Gastroenterology, 142, 219, 10.1053/j.gastro.2011.12.001

Greenhough, 2013, Autolysosomal beta-catenin degradation regulates Wnt-autophagy-p62 crosstalk, EMBO J, 32, 1903, 10.1038/emboj.2013.123

Weis, 2013, The beta-catenin destruction complex, Cold Spring Harb Perspect Biol, 5, a007898, 10.1101/cshperspect.a007898

Kirschner, 2000, Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts, Mol Cell, 5, 523

Cadigan. APC and β-catenin degradation Näthke I. McCartney (ed.). 2009; 656.

Birchmeier, 1998, Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta, Science, 280, 596, 10.1126/science.280.5363.596

Alkalay, 2002, Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway, Genes Dev, 16, 1066, 10.1101/gad.230302

Kikuchi, 1998, Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin, EMBO J, 17, 1371, 10.1093/emboj/17.5.1371

Kinzler, 1992, APC mutations occur early during colorectal tumorigenesis, Nature, 359, 235, 10.1038/359235a0

Yang, 2002, APC as a checkpoint gene: the beginning or the end?, Gastroenterology, 123, 935, 10.1053/gast.2002.35773

Zeng, 2004, LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way, Development, 131, 1663, 10.1242/dev.01117

Nusse, 2004, The Wnt signaling pathway in development and disease, Annu Rev Cell Dev Biol, 20, 781, 10.1146/annurev.cellbio.20.010403.113126

He, 2008, Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions, Development, 135, 367, 10.1242/dev.013540

He, 2004, A mechanism for Wnt coreceptor activation, Mol Cell, 13, 149, 10.1016/S1097-2765(03)00484-2

Liu, 2009, PR55 alpha, a regulatory subunit of PP2A, specifically regulates PP2A-mediated beta-catenin dephosphorylation, J Biol Chem, 284, 22649, 10.1074/jbc.M109.013698

Ha, 2008, Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling, PloS One, 3, e4046, 10.1371/journal.pone.0004046

He, 2009, Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6, PloS One, 4, e4926, 10.1371/journal.pone.0004926

Berns, 2005, Re-evaluating the role of Frat in Wnt-signal transduction, Cell Cycle, 4, 1065

Rosin-Arbesfeld, 2014, Aldolase positively regulates of the canonical Wnt signaling pathway, Mol Cancer, 13, 164, 10.1186/1476-4598-13-164

Moscat, 2015, Repression of Intestinal Stem Cell Function and Tumorigenesis through Direct Phosphorylation of beta-Catenin and Yap by PKCzeta, Cell Rep

Huang, 2015, HSP105 recruits protein phosphatase 2A to dephosphorylate beta-catenin, Mol Cell Biol, 35, 1390, 10.1128/MCB.01307-14

Wu, 2015, DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma as a negative regulator of Wnt/beta-catenin signaling, Oncotarget, 6, 8621, 10.18632/oncotarget.3281

Ni, 2015, RBMY, a novel inhibitor of glycogen synthase kinase 3beta, increases tumor stemness and predicts poor prognosis of hepatocellular carcinoma, Hepatology, 62, 1480, 10.1002/hep.27996

Lu, 2015, Hepatitis B Virus X Protein Stabilizes Cyclin D1 and Increases Cyclin D1 Nuclear Accumulation through ERK-Mediated Inactivation of GSK-3beta, Cancer Pre Res (Phila), 8, 455, 10.1158/1940-6207.CAPR-14-0384

Fuchs, 2000, Wnt/beta-catenin signaling induces the expression and activity of betaTrCP ubiquitin ligase receptor, Mol Cell, 5, 877, 10.1016/S1097-2765(00)80327-5

Cohen, 2008, Jade-1 inhibits Wnt signalling by ubiquitylating beta-catenin and mediates Wnt pathway inhibition by pVHL, Nat Cell Biol, 10, 1208, 10.1038/ncb1781

Reed, 2001, Siah-1, SIP, and Ebi Collaborate In a Novel Pathway for β-catenin Degradation Linked to P53 Rresponses, Mol Cell, 7, 915, 10.1016/S1097-2765(01)00242-8

Rahimi, 2013, c-Cbl, a ubiquitin E3 ligase that targets active beta-catenin: a novel layer of Wnt signaling regulation, J Biol Chem, 288, 23505, 10.1074/jbc.M113.473801

Huang, 2015, Tumour suppressor TRIM33 targets nuclear beta-catenin degradation, Nat Commun, 6, 6156, 10.1038/ncomms7156

Sun, 2014, TRIB2 inhibits Wnt/beta-Catenin/TCF4 signaling through its associated ubiquitin E3 ligases, beta-TrCP, COP1 and Smurf1, in liver cancer cells, FEBS Lett, 588, 4334, 10.1016/j.febslet.2014.09.042

Rosin-Arbesfeld, 2011, The EDD E3 ubiquitin ligase ubiquitinates and up-regulates beta-catenin, Mol Biol Cell, 22, 399, 10.1091/mbc.e10-05-0440

Mao, 2014, The ubiquitin ligase RNF220 enhances canonical Wnt signaling through USP7-mediated deubiquitination of beta-catenin, Mol Cell Biol, 34, 4355, 10.1128/MCB.00731-14

Liu, 2015, Deubiquitinase USP47/UBP64E Regulates beta-Catenin Ubiquitination and Degradation and Plays a Positive Role in Wnt Signaling, Mol Cell Biol, 35, 3301, 10.1128/MCB.00373-15

Kim, 2015, Ubiquitin specific protease 4 positively regulates the WNT/β-catenin signaling in colorectal cancer, Mol Oncol, 9, 1834, 10.1016/j.molonc.2015.06.006

Kikuchi, 2005, Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination, Mol Cell Biol, 25, 9063, 10.1128/MCB.25.20.9063-9072.2005

Smits, 2011, β-Catenin tyrosine 654 phosphorylation increases Wnt signalling and intestinal tumorigenesis, Gut, 60, 1204, 10.1136/gut.2010.233460

Li, 2016, Role of Wnt/beta-catenin pathway in inducing autophagy and apoptosis in multiple myeloma cells, Oncol Lett, 12, 4623, 10.3892/ol.2016.5289

Chun, 2015, Glucose deprivation triggers protein kinase C-dependent beta-catenin proteasomal degradation, J Biol Chem, 290, 9863, 10.1074/jbc.M114.606756

Wang, 2014, Inhibition of atypical protein kinase Ciota induces apoptosis through autophagic degradation of beta-catenin in esophageal cancer cells, Mol Carcinog, 53, 514, 10.1002/mc.22003

Chen, 2010, Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation, Nat Cell Biol, 12, 781, 10.1038/ncb2082

Gumbiner, 1998, Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin, Curr Biol, 8, 181, 10.1016/S0960-9822(98)70082-X

Gumbiner, 2003, Translocation of beta-catenin into the nucleus independent of interactions with FG-rich nucleoporins, Exp Cell Res, 290, 447, 10.1016/S0014-4827(03)00370-7

Darley, 2014, Factors affecting the nuclear localization of beta-catenin in normal and malignant tissue, J Cell Biochem, 115, 1351, 10.1002/jcb.24803

Richardson, 2014, The metastasis suppressor NDRG1 modulates the phosphorylation and nuclear translocation of beta-catenin through mechanisms involving FRAT1 and PAK4, J Cell Sci, 127, 3116, 10.1242/jcs.147835

Habas, 2014, Custos controls beta-catenin to regulate head development during vertebrate embryogenesis, Pro Nat Acad Sci USA, 111, 13099, 10.1073/pnas.1414437111

Liu, 2014, LZTFL1 suppresses gastric cancer cell migration and invasion through regulating nuclear translocation of beta-catenin, J Can Res Clin Oncol, 140, 1997, 10.1007/s00432-014-1753-9

Lee, 2012, XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling, Mol Cell, 45, 619, 10.1016/j.molcel.2011.12.032

Kemler, 2000, The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates, EMBO J, 19, 1839, 10.1093/emboj/19.8.1839

Neuveut, 2004, Acetylation of beta-catenin by p300 regulates beta-catenin-Tcf4 interaction, Mol Cell Biol, 24, 3404, 10.1128/MCB.24.8.3404-3414.2004

Clevers, 2001, The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation, EMBO J, 20, 4935, 10.1093/emboj/20.17.4935

Pestell, 2008, Inhibition of cyclin D1 gene transcription by Brg-1, Cell Cycle, 7, 647, 10.4161/cc.7.5.5446

Hu, 2015, Brg-1 targeting of novel miR550a-5p/RNF43/Wnt signaling axis regulates colorectal cancer metastasis, Oncogene, 35, 651

Pradel, 2000, Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity, EMBO J, 19, 6121, 10.1093/emboj/19.22.6121

Basler, 2002, Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex, Cell, 109, 47, 10.1016/S0092-8674(02)00679-7

Basler, 2005, Pygopus and legless provide essential transcriptional coactivator functions to armadillo/beta-catenin, Curr Biol, 15, 1207, 10.1016/j.cub.2005.05.054

Clevers, 2010, The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/beta-catenin coactivators essential for intestinal homeostasis, PLoS Biol, 8, e1000539, 10.1371/journal.pbio.1000539

Janknecht, 2007, Involvement of RNA helicases p68 and p72 in colon cancer, Cancer Res, 67, 7572, 10.1158/0008-5472.CAN-06-4652

Liu, 2014, SOX10 is a novel oncogene in hepatocellular carcinoma through Wnt/beta-catenin/TCF4 cascade, Tumour Biol, 35, 9935, 10.1007/s13277-014-1893-1

Kung, 2009, The F-box protein beta-TrCP1/Fbw1a interacts with p300 to enhance beta-catenin transcriptional activity, J Biol Chem, 284, 13033, 10.1074/jbc.M901248200

Paraskeva, 2007, Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia, Nat Cell Biol, 9, 210, 10.1038/ncb1534

Park, 2010, HIF-2alpha enhances beta-catenin/TCF-driven transcription by interacting with beta-catenin, Cancer Res, 70, 10101, 10.1158/0008-5472.CAN-10-0505

Kao, 2005, HOXB13 is downregulated in colorectal cancer to confer TCF4-mediated transactivation, Br J Cancer, 92, 2233, 10.1038/sj.bjc.6602631

Kuwata, 2012, Sox4 functions as a positive regulator of beta-catenin signaling through upregulation of TCF4 during morular differentiation of endometrial carcinomas, Lab Invest, 92, 511, 10.1038/labinvest.2011.196

Ito, 2008, RUNX3 attenuates beta-catenin/T cell factors in intestinal tumorigenesis, Cancer Cell, 14, 226, 10.1016/j.ccr.2008.08.004

Finn, 2008, CDK8 is a colorectal cancer oncogene that regulates β-catenin activity, Nature, 455, 547, 10.1038/nature07179

Dyson, 2008, E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8, Nature, 455, 552, 10.1038/nature07310

Li, 2014, TCTP promotes glioma cell proliferation in vitro and in vivo via enhanced beta-catenin/TCF-4 transcription, Neuro Oncol, 16, 217, 10.1093/neuonc/not194

Shih, 2009, Daxx positively modulates beta-catenin/TCF4-mediated transcriptional potential, Biochem Biophys Res Commun, 386, 762, 10.1016/j.bbrc.2009.06.126

Liu, 2010, KLF4 interacts with beta-catenin/TCF4 and blocks p300/CBP recruitment by beta-catenin, Mol Cell Biol, 30, 372, 10.1128/MCB.00063-09

Salomon, 2008, Smad2 functions as a co-activator of canonical Wnt/beta-catenin signaling pathway independent of Smad4 through histone acetyltransferase activity of p300, Cell Signal, 20, 1632, 10.1016/j.cellsig.2008.05.003

Brabletz, 2007, Wnt/beta-catenin signaling in cancer stemness and malignant behavior, Curr Opin Cell Biol, 19, 150, 10.1016/j.ceb.2007.02.007

Monga, 2015, β-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis, Gastroenterology, 148, 1294, 10.1053/j.gastro.2015.02.056

Moon, 2013, WNT signalling pathways as therapeutic targets in cancer, Nat Rev Cancer, 13, 11, 10.1038/nrc3419

Ben-Ze’ev, 2016, Wnt signaling in cancer stem cells and colon cancer metastasis, F1000Res, 11, 5

Gedaly, 2016, Targeting Wnt/beta-catenin pathway in hepatocellular carcinoma treatment, World J Gastroenterol, 22, 823, 10.3748/wjg.v22.i2.823

Srivastava, 2015, Inhibition of beta-catenin signaling suppresses pancreatic tumor growth by disrupting nuclear beta-catenin/TCF-1 complex: critical role of STAT-3, Oncotarget, 6, 11561, 10.18632/oncotarget.3427

Clarke, 2009, K-ras and Wnt signaling synergize to accelerate prostate tumorigenesis in the mouse, Cancer Res, 69, 94, 10.1158/0008-5472.CAN-08-2895

Matusik, 2011, Wnt/beta-catenin activation promotes prostate tumor progression in a mouse model, Oncogene, 30, 1868, 10.1038/onc.2010.560

Moon, 2009, Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model, Pro Nat Acad Sci USA, 106, 1193, 10.1073/pnas.0811902106

Tang, 2010, Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis, Clinical Cancer Res, 16, 2740, 10.1158/1078-0432.CCR-09-2610

Weiss, 2006, A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells, Nat Cell Biol, 8, 1398, 10.1038/ncb1508

Ribas, 2015, Excluding T Cells: Is beta-Catenin the Full Story?, Cancer Cell, 27, 749, 10.1016/j.ccell.2015.05.014

Jung, 2004, Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors, Cancer Res, 64, 1209, 10.1158/0008-5472.CAN-3627-2

Massague, 2016, Metastatic Latency and Immune Evasion through Autocrine Inhibition of WNT, Cell, 165, 45, 10.1016/j.cell.2016.02.025

Gajewski, 2015, Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity, Nature, 523, 231, 10.1038/nature14404

Jiang, 2013, β-Catenin-mediated inhibition of cross-priming: A new mechanism for tumors to evade immunosurveillance, Oncoimmunology, 2, e26920, 10.4161/onci.26920

Varmus, 1988, Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice, Cell, 55, 619, 10.1016/0092-8674(88)90220-6

Cardiff, 2002, Pathway pathology: histological differences between ErbB/Ras and Wnt pathway transgenic mammary tumors, Am J Pathol, 161, 1087, 10.1016/S0002-9440(10)64269-1

Lenz, 2014, The potential of targeting Wnt/beta-catenin in colon cancer, Expert Opin Ther Targets, 18, 611, 10.1517/14728222.2014.906580

Wilson, 2009, Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling, Nature, 461, 614, 10.1038/nature08356

Choo, 2013, A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth, Cancer Res, 73, 3132, 10.1158/0008-5472.CAN-12-4562

von Kries, 2012, A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice, Cancer Res, 72, 2822, 10.1158/0008-5472.CAN-11-3336

Ghidu, 2010, Small-molecule inhibition of Wnt signaling through activation of casein kinase 1alpha, Nat Chem Biol, 6, 829, 10.1038/nchembio.453

Attali, 1991, Sulindac causes regression of rectal polyps in familial adenomatous polyposis, Gastroenterology, 101, 635, 10.1016/0016-5085(91)90519-Q

Zon, 2009, Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration, Cell, 136, 1136, 10.1016/j.cell.2009.01.015

Richel, 2008, Cyclooxygenase-2 inhibition inhibits c-Met kinase activity and Wnt activity in colon cancer, Cancer Res, 68, 1213, 10.1158/0008-5472.CAN-07-5172

Simmen, 2009, Soy isoflavone genistein upregulates epithelial adhesion molecule E-cadherin expression and attenuates beta-catenin signaling in mammary epithelial cells, Carcinogenesis, 30, 331

Sasaguri, 2003, Dictyostelium differentiation-inducing factor-3 activates glycogen synthase kinase-3beta and degrades cyclin D1 in mammalian cells, J Biol Chem, 278, 9663, 10.1074/jbc.M205768200

Yoneda, 1999, β-Catenin can be transported into the nucleus in a Ran-unassisted manner, Mol Biol Cell, 10, 1119, 10.1091/mbc.10.4.1119

Xu, 2012, Targeted disruption of the BCL9/beta-catenin complex inhibits oncogenic Wnt signaling, Sci Transl Med, 4, 148ra117

Ji, 2015, Discovery of Selective Small-Molecule Inhibitors for the beta-Catenin/T-Cell Factor Protein-Protein Interaction through the Optimization of the Acyl Hydrazone Moiety, J Med Chem, 58, 4678, 10.1021/acs.jmedchem.5b00223

Verdine, 2012, Inhibition of oncogenic Wnt signaling through direct targeting of beta-catenin, Pro Nat Acad Sci USA, 109, 17942, 10.1073/pnas.1208396109

Pugh, 2011, Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion, Nat Genet, 43, 964, 10.1038/ng.936

Munoz, 2001, 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, 154, 369, 10.1083/jcb.200102028

Chandraratna, 2003, Adenomatous polyposis coli (APC)-independent regulation of beta-catenin degradation via a retinoid X receptor-mediated pathway, J Biol Chem, 278, 29954, 10.1074/jbc.M304761200

Kahn, 2004, A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected], Pro Nat Acad Sci USA, 101, 12682, 10.1073/pnas.0404875101

Basler, 2010, Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas, Cancer Res, 70, 6619, 10.1158/0008-5472.CAN-10-0148

Chen, 2009, Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer, Nat Chem Biol, 5, 100, 10.1038/nchembio.137

Huang, 2012, FoxM1 and Wnt/β-catenin signaling in glioma stem cells, Cancer Res, 72, 5658, 10.1158/0008-5472.CAN-12-0953

Pferdekamper, 2013, Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974, Proc Natl Acad Sci U S A, 110, 20224, 10.1073/pnas.1314239110