Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Wnt/β-catenin Signaling Inhibitors

Author(s): Xun Zhang, Nazhen Dong and Xiaoyan Hu*

Volume 23, Issue 10, 2023

Published on: 27 March, 2023

Page: [880 - 896] Pages: 17

DOI: 10.2174/1568026623666230303101810

Price: $65

Abstract

The Wnt/β-catenin signaling pathway plays a crucial role in the development, tissue homeostasis, angiogenesis, and carcinogenesis of cancer. Mutations and excessive activation of the Wnt/β-catenin signaling pathway in cancer cells and cancer stem cells lead to drug resistance and recurrence of cancer in patients treated with conventional chemotherapy and radiotherapy. Upregulation of proangiogenic factors is persistently induced by hyperactivated Wnt/β-catenin signaling during tumor angiogenesis. Furthermore, mutations and hyperactivated Wnt/β-catenin signaling are associated with worse outcomes in several human cancers, including breast cancer, cervical cancer, and glioma. Therefore, mutations and hyperactivation of Wnt/β-catenin signaling create challenges and limitations in cancer treatment. Recently, in silico drug design as well as high-throughput assays and experiments have demonstrated the promising anticancer efficacy of chemotherapeutics, such as blocking the cancer cell cycle, inhibiting cancer cell proliferation and endothelial cell angiogenesis, inducing cancer cell apoptosis, removing cancer stem cells, and enhancing immune responses. Compared to conventional chemotherapy and radiotherapy, small-molecule inhibitors are considered the most promising therapeutic strategy for targeting the Wnt/β-catenin signaling pathway. Herein, we review the current small-molecule inhibitors of the Wnt/β-catenin signaling pathway, focusing on Wnt ligands, Wnt receptors, the β-catenin destruction complex, ubiquitin ligases and proteasomal destruction complex, β-catenin, β-catenin-associated transcriptional factors and coactivators, and proangiogenic factors. We describe the structure, mechanisms, and functions of these small molecules during cancer treatment in preclinical and clinical trials. We also review several Wnt/β-catenin inhibitors reported to exhibit anti-angiogenic effects. Finally, we explain various challenges in the targeting of the Wnt/β-catenin signaling pathway in human cancer treatment and suggest potential therapeutic approaches to human cancer.

« Previous Next »
Graphical Abstract

[1]
Logan, C.Y.; Nusse, R. The Wnt signaling pathway in development and disease. Annu. Rev. Cell Dev. Biol., 2004, 20(1), 781-810.
[http://dx.doi.org/10.1146/annurev.cellbio.20.010403.113126] [PMID: 15473860]
[2]
Steinhart, Z.; Angers, S. Wnt signaling in development and tissue homeostasis. Development, 2018, 145(11), ev146589.
[http://dx.doi.org/10.1242/dev.146589] [PMID: 29884654]
[3]
Zerlin, M.; Julius, M.A.; Kitajewski, J. Wnt/Frizzled signaling in angiogenesis. Angiogenesis, 2008, 11(1), 63-69.
[http://dx.doi.org/10.1007/s10456-008-9095-3] [PMID: 18253847]
[4]
Zhan, T.; Rindtorff, N.; Boutros, M. Wnt signaling in cancer. Oncogene, 2017, 36(11), 1461-1473.
[http://dx.doi.org/10.1038/onc.2016.304] [PMID: 27617575]
[5]
Perugorria, M.J.; Olaizola, P.; Labiano, I.; Esparza-Baquer, A.; Marzioni, M.; Marin, J.J.G.; Bujanda, L.; Banales, J.M. Wnt–β-catenin signalling in liver development, health and disease. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(2), 121-136.
[http://dx.doi.org/10.1038/s41575-018-0075-9] [PMID: 30451972]
[6]
Zhong, Z.; Virshup, D.M. Wnt signaling and drug resistance in cancer. Mol. Pharmacol., 2020, 97(2), 72-89.
[http://dx.doi.org/10.1124/mol.119.117978] [PMID: 31787618]
[7]
Schatoff, E.M.; Leach, B.I.; Dow, L.E. WNT signaling and colorectal cancer. Curr. Colorectal Cancer Rep., 2017, 13(2), 101-110.
[http://dx.doi.org/10.1007/s11888-017-0354-9] [PMID: 28413363]
[8]
Nusse, R.; Varmus, H.E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 1982, 31(1), 99-109.
[http://dx.doi.org/10.1016/0092-8674(82)90409-3] [PMID: 6297757]
[9]
Nusse, R.; Brown, A.; Papkoff, J.; Scambler, P.; Shackleford, G.; McMahon, A.; Moon, R.; Varmus, H. A new nomenclature for int-1 and related genes: The Wnt gene family. Cell, 1991, 64(2), 231.
[http://dx.doi.org/10.1016/0092-8674(91)90633-A] [PMID: 1846319]
[10]
Zeng, L.; Fagotto, F.; Zhang, T.; Hsu, W.; Vasicek, T.J.; Perry, W.L., III; Lee, J.J.; Tilghman, S.M.; Gumbiner, B.M.; Costantini, F. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell, 1997, 90(1), 181-192.
[http://dx.doi.org/10.1016/S0092-8674(00)80324-4] [PMID: 9230313]
[11]
Ikeda, S.; Kishida, S.; Yamamoto, H.; Murai, H.; Koyama, S.; Kikuchi, A. 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., 1998, 17(5), 1371-1384.
[http://dx.doi.org/10.1093/emboj/17.5.1371] [PMID: 9482734]
[12]
Liu, C.; Li, Y.; Semenov, M.; Han, C.; Baeg, G.H.; Tan, Y.; Zhang, Z.; Lin, X.; He, X. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell, 2002, 108(6), 837-847.
[http://dx.doi.org/10.1016/S0092-8674(02)00685-2] [PMID: 11955436]
[13]
MacDonald, B.T.; Tamai, K.; He, X. Wnt/beta-catenin signaling: Components, mechanisms, and diseases. Dev. Cell, 2009, 17(1), 9-26.
[http://dx.doi.org/10.1016/j.devcel.2009.06.016] [PMID: 19619488]
[14]
Amit, S.; Hatzubai, A.; Birman, Y.; Andersen, J.S.; Ben-Shushan, E.; Mann, M.; Ben-Neriah, Y.; Alkalay, I. Axin-mediated CKI phosphorylation of β-catenin at Ser 45: A molecular switch for the Wnt pathway. Genes Dev., 2002, 16(9), 1066-1076.
[http://dx.doi.org/10.1101/gad.230302] [PMID: 12000790]
[15]
Latres, E.; Chiaur, D.S.; Pagano, M. The human F box protein β-Trcp associates with the Cul1/Skp1 complex and regulates the stability of β-catenin. Oncogene, 1999, 18(4), 849-854.
[http://dx.doi.org/10.1038/sj.onc.1202653] [PMID: 10023660]
[16]
Aberle, H. Bauer, A.; Stappert, J.; Kispert, A.; Kemler, R. β-catenin is a target for the ubiquitin–proteasome pathway. EMBO J., 1997, 16(13), 3797-3804.
[http://dx.doi.org/10.1093/emboj/16.13.3797] [PMID: 9233789]
[17]
Hurlstone, A.; Clevers, H. New EMBO member’s review: T-cell factors: Turn-ons and turn-offs. EMBO J., 2002, 21(10), 2303-2311.
[http://dx.doi.org/10.1093/emboj/21.10.2303] [PMID: 12006483]
[18]
Billin, A.N.; Thirlwell, H.; Ayer, D.E. Beta-catenin-histone deacetylase interactions regulate the transition of LEF1 from a transcriptional repressor to an activator. Mol. Cell. Biol., 2000, 20(18), 6882-6890.
[http://dx.doi.org/10.1128/MCB.20.18.6882-6890.2000] [PMID: 10958684]
[19]
Cavallo, R.A.; Cox, R.T.; Moline, M.M.; Roose, J.; Polevoy, G.A.; Clevers, H.; Peifer, M.; Bejsovec, A. Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature, 1998, 395(6702), 604-608.
[http://dx.doi.org/10.1038/26982] [PMID: 9783586]
[20]
Roose, J.; Molenaar, M.; Peterson, J.; Hurenkamp, J.; Brantjes, H.; Moerer, P.; van de Wetering, M.; Destrée, O.; Clevers, H. The Xenopus Wnt effector XTcf-3 interacts with groucho-related transcriptional repressors. Nature, 1998, 395(6702), 608-612.
[http://dx.doi.org/10.1038/26989] [PMID: 9783587]
[21]
Chen, G.; Courey, A.J. Groucho/TLE family proteins and transcriptional repression. Gene, 2000, 249(1-2), 1-16.
[http://dx.doi.org/10.1016/S0378-1119(00)00161-X] [PMID: 10831834]
[22]
Brantjes, H.; Roose, J.; van De Wetering, M.; Clevers, H. All Tcf HMG box transcription factors interact with Groucho-related co-repressors. Nucleic Acids Res., 2001, 29(7), 1410-1419.
[http://dx.doi.org/10.1093/nar/29.7.1410] [PMID: 11266540]
[23]
Kawano, Y.; Kypta, R. Secreted antagonists of the Wnt signalling pathway. J. Cell Sci., 2003, 116(13), 2627-2634.
[http://dx.doi.org/10.1242/jcs.00623] [PMID: 12775774]
[24]
Bovolenta, P.; Esteve, P.; Ruiz, J.M.; Cisneros, E.; Lopez-Rios, J. Beyond Wnt inhibition: New functions of secreted Frizzled-related proteins in development and disease. J. Cell Sci., 2008, 121(6), 737-746.
[http://dx.doi.org/10.1242/jcs.026096] [PMID: 18322270]
[25]
Koo, B.K.; Spit, M.; Jordens, I.; Low, T.Y.; Stange, D.E.; van de Wetering, M.; van Es, J.H.; Mohammed, S.; Heck, A.J.R.; Maurice, M.M.; Clevers, H. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature, 2012, 488(7413), 665-669.
[http://dx.doi.org/10.1038/nature11308] [PMID: 22895187]
[26]
Hao, H.X.; Xie, Y.; Zhang, Y.; Charlat, O.; Oster, E.; Avello, M.; Lei, H.; Mickanin, C.; Liu, D.; Ruffner, H.; Mao, X.; Ma, Q.; Zamponi, R.; Bouwmeester, T.; Finan, P.M.; Kirschner, M.W.; Porter, J.A.; Serluca, F.C.; Cong, F. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature, 2012, 485(7397), 195-200.
[http://dx.doi.org/10.1038/nature11019] [PMID: 22575959]
[27]
Jiang, X.; Charlat, O.; Zamponi, R.; Yang, Y.; Cong, F. Dishevelled promotes Wnt receptor degradation through recruitment of ZNRF3/RNF43 E3 ubiquitin ligases. Mol. Cell, 2015, 58(3), 522-533.
[http://dx.doi.org/10.1016/j.molcel.2015.03.015] [PMID: 25891077]
[28]
Bhanot, P.; Brink, M.; Samos, C.H.; Hsieh, J.C.; Wang, Y.; Macke, J.P.; Andrew, D.; Nathans, J.; Nusse, R. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature, 1996, 382(6588), 225-230.
[http://dx.doi.org/10.1038/382225a0] [PMID: 8717036]
[29]
Yang-Snyder, J.; Miller, J.R.; Brown, J.D.; Lai, C.J.; Moon, R.T. A frizzled homolog functions in a vertebrate Wnt signaling pathway. Curr. Biol., 1996, 6(10), 1302-1306.
[http://dx.doi.org/10.1016/S0960-9822(02)70716-1] [PMID: 8939578]
[30]
Kennerdell, J.R.; Carthew, R.W. Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell, 1998, 95(7), 1017-1026.
[http://dx.doi.org/10.1016/S0092-8674(00)81725-0] [PMID: 9875855]
[31]
Wehrli, M.; Dougan, S.T.; Caldwell, K.; O’Keefe, L.; Schwartz, S.; Vaizel-Ohayon, D.; Schejter, E.; Tomlinson, A.; DiNardo, S. Arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature, 2000, 407(6803), 527-530.
[http://dx.doi.org/10.1038/35035110] [PMID: 11029006]
[32]
Tamai, K.; Semenov, M.; Kato, Y.; Spokony, R.; Liu, C.; Katsuyama, Y.; Hess, F.; Saint-Jeannet, J.P.; He, X. LDL-receptor-related proteins in Wnt signal transduction. Nature, 2000, 407(6803), 530-535.
[http://dx.doi.org/10.1038/35035117] [PMID: 11029007]
[33]
He, X.; Semenov, M.; Tamai, K.; Zeng, X. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: Arrows point the way. Development, 2004, 131(8), 1663-1677.
[http://dx.doi.org/10.1242/dev.01117] [PMID: 15084453]
[34]
Zhou, Y.; Nathans, J. Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical Wnt signaling. Dev. Cell, 2014, 31(2), 248-256.
[http://dx.doi.org/10.1016/j.devcel.2014.08.018] [PMID: 25373781]
[35]
Posokhova, E.; Shukla, A.; Seaman, S.; Volate, S.; Hilton, M.B.; Wu, B.; Morris, H.; Swing, D.A.; Zhou, M.; Zudaire, E.; Rubin, J.S.; St Croix, B. GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling. Cell Rep., 2015, 10(2), 123-130.
[http://dx.doi.org/10.1016/j.celrep.2014.12.020] [PMID: 25558062]
[36]
Vanhollebeke, B.; Stone, O.A.; Bostaille, N.; Cho, C.; Zhou, Y.; Maquet, E.; Gauquier, A.; Cabochette, P.; Fukuhara, S.; Mochizuki, N.; Nathans, J.; Stainier, D.Y.R. Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis. eLife, 2015, 4, 06489.
[http://dx.doi.org/10.7554/eLife.06489] [PMID: 26051822]
[37]
Cho, C.; Smallwood, P.M.; Nathans, J. Reck and Gpr124 are essential receptor cofactors for Wnt7a/Wnt7b-specific signaling in mammalian CNS angiogenesis and blood-brain barrier regulation. Neuron, 2017, 95(5), 1056-1073.e5.
[http://dx.doi.org/10.1016/j.neuron.2017.07.031] [PMID: 28803732]
[38]
Gerlach, J.P.; Jordens, I.; Tauriello, D.V.F.; Land-Kuper, V.I.; Bugter, J.M.; Noordstra, I.; van der Kooij, J.; Low, T.Y.; Pimentel-Muiños, F.X.; Xanthakis, D.; Fenderico, N.; Rabouille, C.; Heck, A.J.R.; Egan, D.A.; Maurice, M.M. TMEM59 potentiates Wnt signaling by promoting signalosome formation. Proc. Natl. Acad. Sci. USA, 2018, 115(17), E3996-E4005.
[http://dx.doi.org/10.1073/pnas.1721321115] [PMID: 29632210]
[39]
Metcalfe, C.; Mendoza-Topaz, C.; Mieszczanek, J.; Bienz, M. Stability elements in the LRP6 cytoplasmic tail confer efficient signalling upon DIX-dependent polymerization. J. Cell Sci., 2010, 123(9), 1588-1599.
[http://dx.doi.org/10.1242/jcs.067546] [PMID: 20388731]
[40]
Lien, W.H.; Fuchs, E. Wnt some lose some: Transcriptional governance of stem cells by Wnt/β-catenin signaling. Genes Dev., 2014, 28(14), 1517-1532.
[http://dx.doi.org/10.1101/gad.244772.114] [PMID: 25030692]
[41]
Hecht, A.; Vleminckx, K.; Stemmler, M.P.; van Roy, F.; Kemler, R. The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO J., 2000, 19(8), 1839-1850.
[http://dx.doi.org/10.1093/emboj/19.8.1839] [PMID: 10775268]
[42]
Takemaru, K.I.; Moon, R.T. The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J. Cell Biol., 2000, 149(2), 249-254.
[http://dx.doi.org/10.1083/jcb.149.2.249] [PMID: 10769018]
[43]
Mosimann, C. Hausmann, G.; Basler, K. β-Catenin hits chromatin: Regulation of Wnt target gene activation. Nat. Rev. Mol. Cell Biol., 2009, 10(4), 276-286.
[http://dx.doi.org/10.1038/nrm2654] [PMID: 19305417]
[44]
Townsley, F.M.; Cliffe, A.; Bienz, M. Pygopus and Legless target Armadillo/β-catenin to the nucleus to enable its transcriptional co-activator function. Nat. Cell Biol., 2004, 6(7), 626-633.
[http://dx.doi.org/10.1038/ncb1141] [PMID: 15208637]
[45]
Barker, N.; Hurlstone, A.; Musisi, H.; Miles, A.; Bienz, M.; Clevers, H. The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation. EMBO J., 2001, 20(17), 4935-4943.
[http://dx.doi.org/10.1093/emboj/20.17.4935] [PMID: 11532957]
[46]
de Lau, W.; Barker, N.; Low, T.Y.; Koo, B.K.; Li, V.S.W.; Teunissen, H.; Kujala, P.; Haegebarth, A.; Peters, P.J.; van de Wetering, M.; Stange, D.E.; van Es, J.; Guardavaccaro, D.; Schasfoort, R.B.M.; Mohri, Y.; Nishimori, K.; Mohammed, S.; Heck, A.J.R.; Clevers, H. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature, 2011, 476(7360), 293-297.
[http://dx.doi.org/10.1038/nature10337] [PMID: 21727895]
[47]
Glinka, A.; Dolde, C.; Kirsch, N.; Huang, Y.L.; Kazanskaya, O.; Ingelfinger, D.; Boutros, M.; Cruciat, C.M.; Niehrs, C. LGR4 and LGR5 are R‐spondin receptors mediating Wnt/β‐catenin and Wnt/PCP signalling. EMBO Rep., 2011, 12(10), 1055-1061.
[http://dx.doi.org/10.1038/embor.2011.175] [PMID: 21909076]
[48]
Vermeulen, L.; De Sousa, E.; Melo, F.; van der Heijden, M.; Cameron, K.; de Jong, J.H.; Borovski, T.; Tuynman, J.B.; Todaro, M.; Merz, C.; Rodermond, H.; Sprick, M.R.; Kemper, K.; Richel, D.J.; Stassi, G.; Medema, J.P. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat. Cell Biol., 2010, 12(5), 468-476.
[http://dx.doi.org/10.1038/ncb2048] [PMID: 20418870]
[49]
Khramtsov, A.I.; Khramtsova, G.F.; Tretiakova, M.; Huo, D.; Olopade, O.I.; Goss, K.H. Wnt/beta-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome. Am. J. Pathol., 2010, 176(6), 2911-2920.
[http://dx.doi.org/10.2353/ajpath.2010.091125] [PMID: 20395444]
[50]
Coste, A.L.; Romagnolo, B.; Billuart, P.; Renard, C.A.; Buendia, M.A.; Soubrane, O.; Fabre, M.; Chelly, J.; Beldjord, C.; Kahn, A.; Perret, C. Somatic mutations of the β-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc. Natl. Acad. Sci., 1998, 95(15), 8847-8851.
[http://dx.doi.org/10.1073/pnas.95.15.8847] [PMID: 9671767]
[51]
Anastas, J.N.; Moon, R.T. WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer, 2013, 13(1), 11-26.
[http://dx.doi.org/10.1038/nrc3419] [PMID: 23258168]
[52]
Li, X.; Liang, W.; Liu, J.; Lin, C.; Wu, S.; Song, L.; Yuan, Z. Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer viaactivation of beta-catenin signaling. Breast Cancer Res., 2014, 16(5), 465.
[http://dx.doi.org/10.1186/s13058-014-0465-z] [PMID: 25341494]
[53]
Li, H.; Zhang, W.; Yan, M.; Qiu, J.; Chen, J.; Sun, X.; Chen, X.; Song, L.; Zhang, Y. Nucleolar and spindle associated protein 1 promotes metastasis of cervical carcinoma cells by activating Wnt/β-catenin signaling. J. Exp. Clin. Cancer Res., 2019, 38(1), 33.
[http://dx.doi.org/10.1186/s13046-019-1037-y] [PMID: 30678687]
[54]
Tan, Z.; Song, L.; Wu, W.; Zhou, Y.; Zhu, J.; Wu, G.; Cao, L.; Song, J.; Li, J.; Zhang, W. TRIM14 promotes chemoresistance in gliomas by activating Wnt/β-catenin signaling viastabilizing Dvl2. Oncogene, 2018, 37(40), 5403-5415.
[http://dx.doi.org/10.1038/s41388-018-0344-7] [PMID: 29867201]
[55]
Olsen, J.J.; Pohl, S.Ö.; Deshmukh, A.; Visweswaran, M.; Ward, N.C.; Arfuso, F.; Agostino, M.; Dharmarajan, A. The role of Wnt signalling in angiogenesis. Clin. Biochem. Rev., 2017, 38(3), 131-142.
[PMID: 29332977]
[56]
Pate, K.T.; Stringari, C.; Sprowl-Tanio, S.; Wang, K.; TeSlaa, T.; Hoverter, N.P.; McQuade, M.M.; Garner, C.; Digman, M.A.; Teitell, M.A.; Edwards, R.A.; Gratton, E.; Waterman, M.L. Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer. EMBO J., 2014, 33(13), 1454-1473.
[http://dx.doi.org/10.15252/embj.201488598] [PMID: 24825347]
[57]
Tang, M.K.S.; Yue, P.Y.K.; Ip, P.P.; Huang, R.L.; Lai, H.C.; Cheung, A.N.Y.; Tse, K.Y.; Ngan, H.Y.S.; Wong, A.S.T. Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface. Nat. Commun., 2018, 9(1), 2270.
[http://dx.doi.org/10.1038/s41467-018-04695-7] [PMID: 29891938]
[58]
Reis, M.; Czupalla, C.J.; Ziegler, N.; Devraj, K.; Zinke, J.; Seidel, S.; Heck, R.; Thom, S.; Macas, J.; Bockamp, E.; Fruttiger, M.; Taketo, M.M.; Dimmeler, S.; Plate, K.H.; Liebner, S. Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression. J. Exp. Med., 2012, 209(9), 1611-1627.
[http://dx.doi.org/10.1084/jem.20111580] [PMID: 22908324]
[59]
Han, D.; Cao, C.; Su, Y.; Wang, J.; Sun, J.; Chen, H.; Xu, A. Ginkgo biloba exocarp extracts inhibits angiogenesis and its effects on Wnt/β-catenin-VEGF signaling pathway in Lewis lung cancer. J. Ethnopharmacol., 2016, 192, 406-412.
[http://dx.doi.org/10.1016/j.jep.2016.09.018] [PMID: 27649680]
[60]
Huang, Y.; Zhao, K.; Hu, Y.; Zhou, Y.; Luo, X.; Li, X.; Wei, L.; Li, Z.; You, Q.; Guo, Q.; Lu, N. Wogonoside inhibits angiogenesis in breast cancer viasuppressing Wnt/β-catenin pathway. Mol. Carcinog., 2016, 55(11), 1598-1612.
[http://dx.doi.org/10.1002/mc.22412] [PMID: 26387984]
[61]
Morris, A.; Pagare, P.P.; Li, J.; Zhang, Y. Drug discovery efforts toward inhibitors of canonical Wnt/β-catenin signaling pathway in the treatment of cancer: A composition-of-matter review (2010-2020). Drug Discov. Today, 2022, 27(4), 1115-1127.
[http://dx.doi.org/10.1016/j.drudis.2021.11.014] [PMID: 34800684]
[62]
Voronkov, A.; Krauss, S. Wnt/beta-catenin signaling and small molecule inhibitors. Curr. Pharm. Des., 2013, 19(4), 634-664.
[http://dx.doi.org/10.2174/138161213804581837] [PMID: 23016862]
[63]
Krishnamurthy, N.; Kurzrock, R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat. Rev., 2018, 62, 50-60.
[http://dx.doi.org/10.1016/j.ctrv.2017.11.002] [PMID: 29169144]
[64]
Kaemmerer, E.; Gassler, N. Wnt lipidation and modifiers in intestinal carcinogenesis and cancer. Cancers, 2016, 8(7), 69.
[http://dx.doi.org/10.3390/cancers8070069] [PMID: 27438855]
[65]
Takada, R.; Satomi, Y.; Kurata, T.; Ueno, N.; Norioka, S.; Kondoh, H.; Takao, T.; Takada, S. Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Dev. Cell, 2006, 11(6), 791-801.
[http://dx.doi.org/10.1016/j.devcel.2006.10.003] [PMID: 17141155]
[66]
Hausmann, G.; Bänziger, C.; Basler, K. Helping Wingless take flight: How WNT proteins are secreted. Nat. Rev. Mol. Cell Biol., 2007, 8(4), 331-336.
[http://dx.doi.org/10.1038/nrm2141] [PMID: 17342185]
[67]
van den Heuvel, M.; Harryman-Samos, C.; Klingensmith, J.; Perrimon, N.; Nusse, R. Mutations in the segment polarity genes wingless and porcupine impair secretion of the wingless protein. EMBO J., 1993, 12(13), 5293-5302.
[http://dx.doi.org/10.1002/j.1460-2075.1993.tb06225.x] [PMID: 8262072]
[68]
Liu, J.; Pan, S.; Hsieh, M.H.; Ng, N.; Sun, F.; Wang, T.; Kasibhatla, S.; Schuller, A.G.; Li, A.G.; Cheng, D.; Li, J.; Tompkins, C.; Pferdekamper, A.; Steffy, A.; Cheng, J.; Kowal, C.; Phung, V.; Guo, G.; Wang, Y.; Graham, M.P.; Flynn, S.; Brenner, J.C.; Li, C.; Villarroel, M.C.; Schultz, P.G.; Wu, X.; McNamara, P.; Sellers, W.R.; Petruzzelli, L.; Boral, A.L.; Seidel, H.M.; McLaughlin, M.E.; Che, J.; Carey, T.E.; Vanasse, G.; Harris, J.L. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc. Natl. Acad. Sci. USA, 2013, 110(50), 20224-20229.
[http://dx.doi.org/10.1073/pnas.1314239110] [PMID: 24277854]
[69]
Rodon, J.; Argilés, G.; Connolly, R.M.; Vaishampayan, U.; de Jonge, M.; Garralda, E.; Giannakis, M.; Smith, D.C.; Dobson, J.R.; McLaughlin, M.E.; Seroutou, A.; Ji, Y.; Morawiak, J.; Moody, S.E.; Janku, F. Phase 1 study of single-agent WNT974, a first-in-class Porcupine inhibitor, in patients with advanced solid tumours. Br. J. Cancer, 2021, 125(1), 28-37.
[http://dx.doi.org/10.1038/s41416-021-01389-8] [PMID: 33941878]
[70]
Jiang, X.; Hao, H.X.; Growney, J.D.; Woolfenden, S.; Bottiglio, C.; Ng, N.; Lu, B.; Hsieh, M.H.; Bagdasarian, L.; Meyer, R.; Smith, T.R.; Avello, M.; Charlat, O.; Xie, Y.; Porter, J.A.; Pan, S.; Liu, J.; McLaughlin, M.E.; Cong, F. Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proc. Natl. Acad. Sci., 2013, 110(31), 12649-12654.
[http://dx.doi.org/10.1073/pnas.1307218110] [PMID: 23847203]
[71]
Wang, Y.; Palmer, M.; Jaeger, S.; Bagdasarian, L.; Qiu, S.; Woolfenden, S.; Meyer, R.; Yang, G.; Green, J.; Pan, S.; Liu, J.; Gao, H.; Cao, Z.A.; Myers, A.; McLaughlin, M.E. Abstract 2140: Dual Wnt and EGFR-MAPK dependency of BRAFV600E -mutant colorectal cancer. Cancer Res., 2015, 75(S15), 2140-2140.
[http://dx.doi.org/10.1158/1538-7445.AM2015-2140]
[72]
Xu, Z.; Xu, X.; O’Laoi, R.; Ma, H.; Zheng, J.; Chen, S.; Luo, L.; Hu, Z.; He, S.; Li, J.; Zhang, H.; Zhang, X. Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the ‘reversed’ amide scaffold. Bioorg. Med. Chem., 2016, 24(22), 5861-5872.
[http://dx.doi.org/10.1016/j.bmc.2016.09.041] [PMID: 27692509]
[73]
Proffitt, K.D.; Madan, B.; Ke, Z.; Pendharkar, V.; Ding, L.; Lee, M.A.; Hannoush, R.N.; Virshup, D.M. Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Res., 2013, 73(2), 502-507.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-2258] [PMID: 23188502]
[74]
Cheng, Y.; Phoon, Y.P.; Jin, X.; Chong, S.Y.S.; Ip, J.C.Y.; Wong, B.W.Y.; Lung, M.L. Wnt-C59 arrests stemness and suppresses growth of nasopharyngeal carcinoma in mice by inhibiting the Wnt pathway in the tumor microenvironment. Oncotarget, 2015, 6(16), 14428-14439.
[http://dx.doi.org/10.18632/oncotarget.3982] [PMID: 25980501]
[75]
Madan, B.; Ke, Z.; Harmston, N.; Ho, S.Y.; Frois, A.O.; Alam, J.; Jeyaraj, D.A.; Pendharkar, V.; Ghosh, K.; Virshup, I.H.; Manoharan, V.; Ong, E.H.Q.; Sangthongpitag, K.; Hill, J.; Petretto, E.; Keller, T.H.; Lee, M.A.; Matter, A.; Virshup, D.M. Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene, 2016, 35(17), 2197-2207.
[http://dx.doi.org/10.1038/onc.2015.280] [PMID: 26257057]
[76]
Zhong, Z.; Sepramaniam, S.; Chew, X.H.; Wood, K.; Lee, M.A.; Madan, B.; Virshup, D.M. PORCN inhibition synergizes with PI3K/mTOR inhibition in Wnt-addicted cancers. Oncogene, 2019, 38(40), 6662-6677.
[http://dx.doi.org/10.1038/s41388-019-0908-1] [PMID: 31391551]
[77]
Shah, K.; Panchal, S.; Patel, B. Porcupine inhibitors: Novel and emerging anti-cancer therapeutics targeting the Wnt signaling pathway. Pharmacol. Res., 2021, 167, 05532.
[http://dx.doi.org/10.1016/j.phrs.2021.105532] [PMID: 33677106]
[78]
Woodcock, S.; Bhamra, I.; Jones, C.; Cook, A.E.; Eagle, C.; Phillips, C. Abstract 3874: Efficacy of the Wnt/Beta-Catenin pathway inhibitor RXC004 in genetically-defined models of cancer Cancer Res., 2019, 79(13_Supplement)(Suppl.), 3874-3874.
[http://dx.doi.org/10.1158/1538-7445.AM2019-3874]
[79]
Phillips, C.; Woodcock, S.; Eagle, C.; Saunders, A.; Tilston, C.; Bhamra, I.; Armer, R. Abstract 998: Mechanism of action of RXC004, a Wnt pathway inhibitor, in genetically-defined models of cancer. Cancer Res., 2021, 81(S13), 998-998.
[http://dx.doi.org/10.1158/1538-7445.AM2021-998]
[80]
Bhamra, I.; Armer, R.; Bingham, M.; Eagle, C.; Cook, A.E.; Phillips, C.; Woodcock, S. Abstract 3764: Porcupine inhibitor RXC004 enhances immune response in pre-clinical models of cancer. Cancer Res., 2018, 78(S13), 3764-3764.
[http://dx.doi.org/10.1158/1538-7445.AM2018-3764]
[81]
Phillips, C.; Bhamra, I.; Eagle, C.; Cook, A.E.; Jones, C.; Woodcock, S. Abstract 506: Wnt/â-Catenin pathway inhibitor RXC004 enhances the immunity of pre-clinical models of cancer. Cancer Res., 2019, 79(S13), 506-506.
[http://dx.doi.org/10.1158/1538-7445.AM2019-506]
[82]
Zeng, X.; Huang, H.; Tamai, K.; Zhang, X.; Harada, Y.; Yokota, C.; Almeida, K.; Wang, J.; Doble, B.; Woodgett, J.; Wynshaw-Boris, A.; Hsieh, J.C.; He, X. Initiation of Wnt signaling: Control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions. Development, 2008, 135(2), 367-375.
[http://dx.doi.org/10.1242/dev.013540] [PMID: 18077588]
[83]
Davidson, G. LRPs in WNT signalling. Handb. Exp. Pharmacol., 2021, 269, 45-73.
[http://dx.doi.org/10.1007/164_2021_526] [PMID: 34490514]
[84]
Schulte, G.; Bryja, V. The Frizzled family of unconventional G-protein-coupled receptors. Trends Pharmacol. Sci., 2007, 28(10), 518-525.
[http://dx.doi.org/10.1016/j.tips.2007.09.001] [PMID: 17884187]
[85]
Foord, S.M.; Bonner, T.I.; Neubig, R.R.; Rosser, E.M.; Pin, J.P.; Davenport, A.P.; Spedding, M.; Harmar, A.J. International union of pharmacology. XLVI. G protein-coupled receptor list. Pharmacol. Rev., 2005, 57(2), 279-288.
[http://dx.doi.org/10.1124/pr.57.2.5] [PMID: 15914470]
[86]
Schulte, G. International union of basic and clinical pharmacology. LXXX. The class frizzled receptors. Pharmacol. Rev., 2010, 62(4), 632-667.
[http://dx.doi.org/10.1124/pr.110.002931] [PMID: 21079039]
[87]
Zeng, C.M.; Chen, Z.; Fu, L. Frizzled receptors as potential therapeutic targets in human cancers. Int. J. Mol. Sci., 2018, 19(5), 1543.
[http://dx.doi.org/10.3390/ijms19051543] [PMID: 29789460]
[88]
Tomizawa, M.; Shinozaki, F.; Motoyoshi, Y.; Sugiyama, T.; Yamamoto, S.; Ishige, N. Gastric cancer cell proliferation is suppressed by frizzled-2 short hairpin RNA. Int. J. Oncol., 2015, 46(3), 1018-1024.
[http://dx.doi.org/10.3892/ijo.2015.2830] [PMID: 25586465]
[89]
Flanagan, D.J.; Barker, N.; Costanzo, N.S.D.; Mason, E.A.; Gurney, A.; Meniel, V.S.; Koushyar, S.; Austin, C.R.; Ernst, M.; Pearson, H.B.; Boussioutas, A.; Clevers, H.; Phesse, T.J.; Vincan, E. Frizzled-7 is required for wnt signaling in gastric tumors with and without Apc mutations. Cancer Res., 2019, 79(5), 970-981.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2095] [PMID: 30622113]
[90]
Chen, W.; Liu, Z.; Mai, W.; Xiao, Y.; You, X.; Qin, L. FZD8 indicates a poor prognosis and promotes gastric cancer invasion and metastasis viab-catenin signaling pathway. Ann. Clin. Lab. Sci., 2020, 50(1), 13-23.
[PMID: 32161008]
[91]
Li, G.; Su, Q.; Liu, H.; Wang, D.; Zhang, W.; Lu, Z.; Chen, Y.; Huang, X.; Li, W.; Zhang, C.; He, Y.; Fu, L.; Bi, J. Frizzled7 promotes epithelial-to-mesenchymal transition and stemness viaactivating canonical Wnt/β-catenin pathway in gastric cancer. Int. J. Biol. Sci., 2018, 14(3), 280-293.
[http://dx.doi.org/10.7150/ijbs.23756] [PMID: 29559846]
[92]
Murillo-Garzón, V.; Gorroño-Etxebarria, I.; Åkerfelt, M.; Puustinen, M.C.; Sistonen, L.; Nees, M.; Carton, J.; Waxman, J.; Kypta, R.M. Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer. Nat. Commun., 2018, 9(1), 1747.
[http://dx.doi.org/10.1038/s41467-018-04042-w] [PMID: 29717114]
[93]
Dong, D.; Na, L.; Zhou, K.; Wang, Z.; Sun, Y.; Zheng, Q.; Gao, J.; Zhao, C.; Wang, W. FZD5 prevents epithelial-mesenchymal transition in gastric cancer. Cell Commun. Signal., 2021, 19(1), 21.
[http://dx.doi.org/10.1186/s12964-021-00708-z] [PMID: 33618713]
[94]
Chen, M.; Wang, J.; Lu, J.; Bond, M.C.; Ren, X.R.; Lyerly, H.K.; Barak, L.S.; Chen, W. The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling. Biochemistry, 2009, 48(43), 10267-10274.
[http://dx.doi.org/10.1021/bi9009677] [PMID: 19772353]
[95]
Osada, T.; Chen, M.; Yang, X.Y.; Spasojevic, I.; Vandeusen, J.B.; Hsu, D.; Clary, B.M.; Clay, T.M.; Chen, W.; Morse, M.A.; Lyerly, H.K. Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations. Cancer Res., 2011, 71(12), 4172-4182.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-3978] [PMID: 21531761]
[96]
Schweizer, M.T.; Haugk, K.; McKiernan, J.S.; Gulati, R.; Cheng, H.H.; Maes, J.L.; Dumpit, R.F.; Nelson, P.S.; Montgomery, B.; McCune, J.S.; Plymate, S.R.; Yu, E.Y. A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer. PLoS One, 2018, 13(6), 0198389.
[http://dx.doi.org/10.1371/journal.pone.0198389] [PMID: 29856824]
[97]
Li, Y.; Bu, G. LRP5/6 in Wnt signaling and tumorigenesis. Future Oncol., 2005, 1(5), 673-681.
[http://dx.doi.org/10.2217/14796694.1.5.673] [PMID: 16556044]
[98]
Goel, S.; Chin, E.N.; Fakhraldeen, S.A.; Berry, S.M.; Beebe, D.J.; Alexander, C.M. Both LRP5 and LRP6 receptors are required to respond to physiological Wnt ligands in mammary epithelial cells and fibroblasts. J. Biol. Chem., 2012, 287(20), 16454-16466.
[http://dx.doi.org/10.1074/jbc.M112.362137] [PMID: 22433869]
[99]
MacDonald, B.T.; He, X. Frizzled and LRP5/6 receptors for Wnt/β-catenin signaling. Cold Spring Harb. Perspect. Biol., 2012, 4(12), 007880.
[http://dx.doi.org/10.1101/cshperspect.a007880] [PMID: 23209147]
[100]
Mi, K.; Johnson, G.V.W. Role of the intracellular domains of LRP5 and LRP6 in activating the Wnt canonical pathway. J. Cell. Biochem., 2005, 95(2), 328-338.
[http://dx.doi.org/10.1002/jcb.20400] [PMID: 15778991]
[101]
Joeng, K.S.; Schumacher, C.A.; Zylstra-Diegel, C.R.; Long, F.; Williams, B.O. Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Dev. Biol., 2011, 359(2), 222-229.
[http://dx.doi.org/10.1016/j.ydbio.2011.08.020] [PMID: 21924256]
[102]
Toomes, C.; Bottomley, H.M.; Jackson, R.M.; Towns, K.V.; Scott, S.; Mackey, D.A.; Craig, J.E.; Jiang, L.; Yang, Z.; Trembath, R.; Woodruff, G.; Gregory-Evans, C.Y.; Gregory-Evans, K.; Parker, M.J.; Black, G.C.M.; Downey, L.M.; Zhang, K.; Inglehearn, C.F. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am. J. Hum. Genet., 2004, 74(4), 721-730.
[http://dx.doi.org/10.1086/383202] [PMID: 15024691]
[103]
Zhou, Y.; Wang, Y.; Tischfield, M.; Williams, J.; Smallwood, P.M.; Rattner, A.; Taketo, M.M.; Nathans, J. Canonical WNT signaling components in vascular development and barrier formation. J. Clin. Invest., 2014, 124(9), 3825-3846.
[http://dx.doi.org/10.1172/JCI76431] [PMID: 25083995]
[104]
Wang, X.; Adhikari, N.; Li, Q.; Hall, J.L. LDL receptor-related protein LRP6 regulates proliferation and survival through the Wnt cascade in vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol., 2004, 287(6), H2376-H2383.
[http://dx.doi.org/10.1152/ajpheart.01173.2003] [PMID: 15271658]
[105]
Gong, Y.; Slee, R.B.; Fukai, N.; Rawadi, G.; Roman-Roman, S.; Reginato, A.M.; Wang, H.; Cundy, T.; Glorieux, F.H.; Lev, D.; Zacharin, M.; Oexle, K.; Marcelino, J.; Suwairi, W.; Heeger, S.; Sabatakos, G.; Apte, S.; Adkins, W.N.; Allgrove, J.; Arslan-Kirchner, M.; Batch, J.A.; Beighton, P.; Black, G.C.M.; Boles, R.G.; Boon, L.M.; Borrone, C.; Brunner, H.G.; Carle, G.F.; Dallapiccola, B.; De Paepe, A.; Floege, B.; Halfhide, M.L.; Hall, B.; Hennekam, R.C.; Hirose, T.; Jans, A.; Jüppner, H.; Kim, C.A.; Keppler-Noreuil, K.; Kohlschuetter, A.; LaCombe, D.; Lambert, M.; Lemyre, E.; Letteboer, T.; Peltonen, L.; Ramesar, R.S.; Romanengo, M.; Somer, H.; Steichen-Gersdorf, E.; Steinmann, B.; Sullivan, B.; Superti-Furga, A.; Swoboda, W.; van den Boogaard, M.J.; Van Hul, W.; Vikkula, M.; Votruba, M.; Zabel, B.; Garcia, T.; Baron, R.; Olsen, B.R.; Warman, M.L. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell, 2001, 107(4), 513-523.
[http://dx.doi.org/10.1016/S0092-8674(01)00571-2] [PMID: 11719191]
[106]
Boyden, L.M.; Mao, J.; Belsky, J.; Mitzner, L.; Farhi, A.; Mitnick, M.A.; Wu, D.; Insogna, K.; Lifton, R.P. High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med., 2002, 346(20), 1513-1521.
[http://dx.doi.org/10.1056/NEJMoa013444] [PMID: 12015390]
[107]
Little, R.D.; Folz, C.; Manning, S.P.; Swain, P.M.; Zhao, S-C.; Eustace, B.; Lappe, M.M.; Spitzer, L.; Zweier, S.; Braunschweiger, K.; Benchekroun, Y.; Hu, X.; Adair, R.; Chee, L.; FitzGerald, M.G.; Tulig, C.; Caruso, A.; Tzellas, N.; Bawa, A.; Franklin, B.; McGuire, S.; Nogues, X.; Gong, G.; Allen, K.M.; Anisowicz, A.; Morales, A.J.; Lomedico, P.T.; Recker, S.M.; Van Eerdewegh, P.; Recker, R.R.; Carulli, J.P.; Del Mastro, R.G.; Dupuis, J.; Osborne, M.; Johnson, M.L. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am. J. Hum. Genet., 2002, 70(1), 11-19.
[http://dx.doi.org/10.1086/338450] [PMID: 11741193]
[108]
Ren, Q.; Chen, J.; Liu, Y. LRP5 and LRP6 in Wnt signaling: Similarity and divergence. Front. Cell Dev. Biol., 2021, 9, 70960.
[http://dx.doi.org/10.3389/fcell.2021.670960] [PMID: 34026761]
[109]
Jeong, W.; Jho, E. Regulation of the low-density lipoprotein receptor-related protein LRP6 and its association with disease: Wnt/β-catenin signaling and beyond. Front. Cell Dev. Biol., 2021, 9, 14330.
[http://dx.doi.org/10.3389/fcell.2021.714330] [PMID: 34589484]
[110]
Li, Y.; Lu, W.; He, X.; Schwartz, A.L.; Bu, G. LRP6 expression promotes cancer cell proliferation and tumorigenesis by altering β-catenin subcellular distribution. Oncogene, 2004, 23(56), 9129-9135.
[http://dx.doi.org/10.1038/sj.onc.1208123] [PMID: 15516984]
[111]
Raisch, J.; Côté-Biron, A.; Rivard, N. A role for the WNT co-receptor LRP6 in pathogenesis and therapy of epithelial cancers. Cancers, 2019, 11(8), 1162.
[http://dx.doi.org/10.3390/cancers11081162] [PMID: 31412666]
[112]
Li, Y.; Chen, J.; Lu, W.; McCormick, L.M.; Wang, J.; Bu, G. Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding. J. Cell Sci., 2005, 118(22), 5305-5314.
[http://dx.doi.org/10.1242/jcs.02651] [PMID: 16263759]
[113]
Lu, W.; Liu, C.C.; Thottassery, J.V.; Bu, G.; Li, Y. Mesd is a universal inhibitor of Wnt coreceptors LRP5 and LRP6 and blocks Wnt/beta-catenin signaling in cancer cells. Biochemistry, 2010, 49(22), 4635-4643.
[http://dx.doi.org/10.1021/bi1001486] [PMID: 20446724]
[114]
Ahn, V.E.; Chu, M.L.H.; Choi, H.J.; Tran, D.; Abo, A.; Weis, W.I. Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Dev. Cell, 2011, 21(5), 862-873.
[http://dx.doi.org/10.1016/j.devcel.2011.09.003] [PMID: 22000856]
[115]
Cheng, Z.; Biechele, T.; Wei, Z.; Morrone, S.; Moon, R.T.; Wang, L.; Xu, W. Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat. Struct. Mol. Biol., 2011, 18(11), 1204-1210.
[http://dx.doi.org/10.1038/nsmb.2139] [PMID: 21984209]
[116]
Niehrs, C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene, 2006, 25(57), 7469-7481.
[http://dx.doi.org/10.1038/sj.onc.1210054] [PMID: 17143291]
[117]
Wang, X.; Goode, E.L.; Fredericksen, Z.S.; Vierkant, R.A.; Pankratz, V.S.; Liu-Mares, W.; Rider, D.N.; Vachon, C.M.; Cerhan, J.R.; Olson, J.E.; Couch, F.J. Association of genetic variation in genes implicated in the beta-catenin destruction complex with risk of breast cancer. Cancer Epidemiol. Biomarkers Prev., 2008, 17(8), 2101-2108.
[http://dx.doi.org/10.1158/1055-9965.EPI-08-0134] [PMID: 18708403]
[118]
Huang, S.M.A.; Mishina, Y.M.; Liu, S.; Cheung, A.; Stegmeier, F.; Michaud, G.A.; Charlat, O.; Wiellette, E.; Zhang, Y.; Wiessner, S.; Hild, M.; Shi, X.; Wilson, C.J.; Mickanin, C.; Myer, V.; Fazal, A.; Tomlinson, R.; Serluca, F.; Shao, W.; Cheng, H.; Shultz, M.; Rau, C.; Schirle, M.; Schlegl, J.; Ghidelli, S.; Fawell, S.; Lu, C.; Curtis, D.; Kirschner, M.W.; Lengauer, C.; Finan, P.M.; Tallarico, J.A.; Bouwmeester, T.; Porter, J.A.; Bauer, A.; Cong, F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature, 2009, 461(7264), 614-620.
[http://dx.doi.org/10.1038/nature08356] [PMID: 19759537]
[119]
Kim, M. Novel insight into the function of tankyrase. (Review). Oncol. Lett., 2018, 16(6), 6895-6902.
[http://dx.doi.org/10.3892/ol.2018.9551] [PMID: 30546421]
[120]
Lai, K.K.Y.; Kahn, M. Pharmacologically targeting the WNT/β-catenin signaling cascade: Avoiding the sword of damocles. Handb. Exp. Pharmacol., 2021, 269, 383-422.
[http://dx.doi.org/10.1007/164_2021_523] [PMID: 34463849]
[121]
Mygland, L.; Brinch, S.A.; Strand, M.F.; Olsen, P.A.; Aizenshtadt, A.; Lund, K.; Solberg, N.T.; Lycke, M.; Thorvaldsen, T.E.; Espada, S.; Misaghian, D.; Page, C.M.; Agafonov, O.; Nygård, S.; Chi, N.W.; Lin, E.; Tan, J.; Yu, Y.; Costa, M.; Krauss, S.; Waaler, J. Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines. iScience, 2021, 24(7), 02807.
[http://dx.doi.org/10.1016/j.isci.2021.102807] [PMID: 34337362]
[122]
Plummer, R.; Dua, D.; Cresti, N.; Drew, Y.; Stephens, P.; Foegh, M.; Knudsen, S.; Sachdev, P.; Mistry, B.M.; Dixit, V.; McGonigle, S.; Hall, N.; Matijevic, M.; McGrath, S.; Sarker, D. First-in-human study of the PARP/tankyrase inhibitor E7449 in patients with advanced solid tumours and evaluation of a novel drug-response predictor. Br. J. Cancer, 2020, 123(4), 525-533.
[http://dx.doi.org/10.1038/s41416-020-0916-5] [PMID: 32523090]
[123]
Marin, O.; Bustos, V.H.; Cesaro, L.; Meggio, F.; Pagano, M.A.; Antonelli, M.; Allende, C.C.; Pinna, L.A.; Allende, J.E. A noncanonical sequence phosphorylated by casein kinase 1 in β-catenin may play a role in casein kinase 1 targeting of important signaling proteins. Proc. Natl. Acad. Sci. USA, 2003, 100(18), 10193-10200.
[http://dx.doi.org/10.1073/pnas.1733909100] [PMID: 12925738]
[124]
Thorne, C.A.; Hanson, A.J.; Schneider, J.; Tahinci, E.; Orton, D.; Cselenyi, C.S.; Jernigan, K.K.; Meyers, K.C.; Hang, B.I.; Waterson, A.G.; Kim, K.; Melancon, B.; Ghidu, V.P.; Sulikowski, G.A.; LaFleur, B.; Salic, A.; Lee, L.A.; Miller, D.M., III; Lee, E. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α. Nat. Chem. Biol., 2010, 6(11), 829-836.
[http://dx.doi.org/10.1038/nchembio.453] [PMID: 20890287]
[125]
Xiong, Y.; Zhou, L.; Su, Z.; Song, J.; Sun, Q.; Liu, S.S.; Xia, Y.; Wang, Z.; Lu, D. Longdaysin inhibits Wnt/β-catenin signaling and exhibits antitumor activity against breast cancer. OncoTargets Ther., 2019, 12, 993-1005.
[http://dx.doi.org/10.2147/OTT.S193024] [PMID: 30787621]
[126]
Borgal, L.; Rinschen, M.M.; Dafinger, C.; Hoff, S.; Reinert, M.J.; Lamkemeyer, T.; Lienkamp, S.S.; Benzing, T.; Schermer, B. Casein kinase 1 α phosphorylates the Wnt regulator Jade-1 and modulates its activity. J. Biol. Chem., 2014, 289(38), 26344-26356.
[http://dx.doi.org/10.1074/jbc.M114.562165] [PMID: 25100726]
[127]
Wu, D.; Pan, W. GSK3: A multifaceted kinase in Wnt signaling. Trends Biochem. Sci., 2010, 35(3), 161-168.
[http://dx.doi.org/10.1016/j.tibs.2009.10.002] [PMID: 19884009]
[128]
Kisoh, K.; Hayashi, H.; Itoh, T.; Asada, M.; Arai, M.; Yuan, B.; Tanonaka, K.; Takagi, N. Involvement of GSK-3β phosphorylation through PI3-K/Akt in Cerebral ischemia-induced neurogenesis in rats. Mol. Neurobiol., 2017, 54(10), 7917-7927.
[http://dx.doi.org/10.1007/s12035-016-0290-8] [PMID: 27866373]
[129]
Piao, S.; Lee, S.H.; Kim, H.; Yum, S.; Stamos, J.L.; Xu, Y.; Lee, S.J.; Lee, J.; Oh, S.; Han, J.K.; Park, B.J.; Weis, W.I.; Ha, N.C. Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling. PLoS One, 2008, 3(12), 4046.
[http://dx.doi.org/10.1371/journal.pone.0004046] [PMID: 19107203]
[130]
Valenta, T.; Hausmann, G.; Basler, K. The many faces and functions of β-catenin. EMBO J., 2012, 31(12), 2714-2736.
[http://dx.doi.org/10.1038/emboj.2012.150] [PMID: 22617422]
[131]
Hülsken, J.; Birchmeier, W.; Behrens, J. E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. J. Cell Biol., 1994, 127(6), 2061-2069.
[http://dx.doi.org/10.1083/jcb.127.6.2061] [PMID: 7806582]
[132]
McCrea, P.D.; Turck, C.W.; Gumbiner, B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science, 1991, 254(5036), 1359-1361.
[http://dx.doi.org/10.1126/science.1962194] [PMID: 1962194]
[133]
Moon, R.T.; Kimelman, D. From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus. BioEssays, 1998, 20(7), 536-546.
[http://dx.doi.org/10.1002/(SICI)1521-1878(199807)20:7<536:AID-BIES4>3.0.CO;2-I] [PMID: 9723002]
[134]
Peifer, M.; Polakis, P. Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus. Science, 2000, 287(5458), 1606-1609.
[http://dx.doi.org/10.1126/science.287.5458.1606] [PMID: 10733430]
[135]
Xing, Y.; Takemaru, K.; Liu, J.; Berndt, J.D.; Zheng, J.J.; Moon, R.T.; Xu, W. Crystal structure of a full-length beta-catenin. Structure, 2008, 16(3), 478-487.
[http://dx.doi.org/10.1016/j.str.2007.12.021] [PMID: 18334222]
[136]
Vleminckx, K.; Kemler, R.; Hecht, A. The C-terminal transactivation domain of β-catenin is necessary and sufficient for signaling by the LEF-1/β-catenin complex in Xenopus laevis. Mech. Dev., 1999, 81(1-2), 65-74.
[http://dx.doi.org/10.1016/S0925-4773(98)00225-1] [PMID: 10330485]
[137]
Xu, W.; Kimelman, D. Mechanistic insights from structural studies of β-catenin and its binding partners. J. Cell Sci., 2007, 120(19), 3337-3344.
[http://dx.doi.org/10.1242/jcs.013771] [PMID: 17881495]
[138]
Dar, M.S. Singh, P.; Mir, R.A.; Dar, M.J. Βeta-catenin N-terminal domain: An enigmatic region prone to cancer causing mutations. Mutat. Res. Rev. Mutat. Res., 2017, 773, 122-133.
[http://dx.doi.org/10.1016/j.mrrev.2017.06.001] [PMID: 28927523]
[139]
Clevers, H.; Nusse, R. Wnt/β-catenin signaling and disease. Cell, 2012, 149(6), 1192-1205.
[http://dx.doi.org/10.1016/j.cell.2012.05.012] [PMID: 22682243]
[140]
Behrens, J.; von Kries, J.P.; Kühl, M.; Bruhn, L.; Wedlich, D.; Grosschedl, R.; Birchmeier, W. Functional interaction of β-catenin with the transcription factor LEF-1. Nature, 1996, 382(6592), 638-642.
[http://dx.doi.org/10.1038/382638a0] [PMID: 8757136]
[141]
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. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell, 1997, 88(6), 789-799.
[http://dx.doi.org/10.1016/S0092-8674(00)81925-X] [PMID: 9118222]
[142]
Hrckulak, D.; Kolar, M.; Strnad, H.; Korinek, V. TCF/LEF transcription factors: An update from the internet resources. Cancers, 2016, 8(7), 70.
[http://dx.doi.org/10.3390/cancers8070070] [PMID: 27447672]
[143]
Merrill, B.J.; Pasolli, H.A.; Polak, L.; Rendl, M.; García-García, M.J.; Anderson, K.V.; Fuchs, E. Tcf3: A transcriptional regulator of axis induction in the early embryo. Development, 2004, 131(2), 263-274.
[http://dx.doi.org/10.1242/dev.00935] [PMID: 14668413]
[144]
Lepourcelet, M.; Chen, Y.N.P.; France, D.S.; Wang, H.; Crews, P.; Petersen, F.; Bruseo, C.; Wood, A.W.; Shivdasani, R.A. Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex. Cancer Cell, 2004, 5(1), 91-102.
[http://dx.doi.org/10.1016/S1535-6108(03)00334-9] [PMID: 14749129]
[145]
Minke, K.S.; Staib, P.; Puetter, A.; Gehrke, I.; Gandhirajan, R.K.; Schlösser, A.; Schmitt, E.K.; Hallek, M.; Kreuzer, K.A. Small molecule inhibitors of WNT signaling effectively induce apoptosis in acute myeloid leukemia cells. Eur. J. Haematol., 2009, 82(3), 165-175.
[http://dx.doi.org/10.1111/j.1600-0609.2008.01188.x] [PMID: 19067737]
[146]
Wei, W.; Chua, M.S.; Grepper, S.; So, S. Small molecule antagonists of Tcf4/beta-catenin complex inhibit the growth of HCC cells in vitro and in vivo. Int. J. Cancer, 2010, 126(10), 2426-2436.
[PMID: 19662654]
[147]
Ewan, K. Pająk, B.; Stubbs, M.; Todd, H.; Barbeau, O.; Quevedo, C.; Botfield, H.; Young, R.; Ruddle, R.; Samuel, L.; Battersby, A.; Raynaud, F.; Allen, N.; Wilson, S.; Latinkic, B.; Workman, P.; McDonald, E.; Blagg, J.; Aherne, W.; Dale, T. A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription. Cancer Res., 2010, 70(14), 5963-5973.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1028] [PMID: 20610623]
[148]
Pak, S.; Park, S.; Kim, Y.; Park, J.H.; Park, C.H.; Lee, K.J.; Kim, C.; Ahn, H. The small molecule WNT/β-catenin inhibitor CWP232291 blocks the growth of castration-resistant prostate cancer by activating the endoplasmic reticulum stress pathway. J. Exp. Clin. Cancer Res., 2019, 38(1), 342.
[http://dx.doi.org/10.1186/s13046-019-1342-5] [PMID: 31387608]
[149]
Park, J.W.; Park, J.M.; Green, J.E.; Kim, H.K. Long-term effect of Wnt/β-catenin small molecule inhibitor CWP232291 on intestinal carcinogenesis in novel GEM model deficient in Smad4 and p53. J. Clin. Oncol., 2016, 34(S4), 594-594.
[http://dx.doi.org/10.1200/jco.2016.34.4_suppl.594]
[150]
Park, J.W.; Um, H.; Yang, H.; Cha, J.Y.; Lee, K.J.; Kim, H.K. CWP232291, a Wnt/β-catenin inhibitor, to suppress the growth and development of gastrointestinal cancers. J. Clin. Oncol., 2017, 35(S15), e15534-e15534.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.e15534]
[151]
Lee, J.H.; Faderl, S.; Pagel, J.M.; Jung, C.W.; Yoon, S.S.; Pardanani, A.D.; Becker, P.S.; Lee, H.; Choi, J.; Lee, K.; Kim, M.; Cortes, J.E. Phase 1 study of CWP232291 in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome. Blood Adv., 2020, 4(9), 2032-2043.
[http://dx.doi.org/10.1182/bloodadvances.2019000757] [PMID: 32396615]
[152]
Manasanch, E.E.; Yoon, S-S.; Min, C-K.; Kim, J.S.; Shain, K.H.; Hauptschein, R.; Choi, J.E.; Lee, K-J. Interim results from the phase 1a/1b dose-finding study of CWP232291 (CWP291) in relapsed or refractory myeloma (RRMM) alone or in combination with lenalidomide and dexamethasone. Blood, 2017, 130(S1), 3091-3091. [https://www.sciencedirect.com/science/article/pii/S0006497119836078
[153]
Park, J.W.; Seo, M.J.; Cho, K.S.; Kook, M.C.; Jeong, J.M.; Roh, S.G.; Cho, S.Y.; Cheon, J.H.; Kim, H.K. Smad4 and p53 synergize in suppressing autochthonous intestinal cancer. Cancer Med., 2022, 11(9), 1925-1936.
[http://dx.doi.org/10.1002/cam4.4533] [PMID: 35274815]
[154]
Huang, Z.; Zhang, M.; Burton, S.D.; Katsakhyan, L.N.; Ji, H. Targeting the Tcf4 G13ANDE17 binding site to selectively disrupt β-catenin/T-cell factor protein-protein interactions. ACS Chem. Biol., 2014, 9(1), 193-201.
[http://dx.doi.org/10.1021/cb400795x] [PMID: 24191653]
[155]
Catrow, J.L.; Zhang, Y.; Zhang, M.; Ji, H. Discovery of selective small-molecule inhibitors for the β-Catenin/T-cell factor protein–protein interaction through the optimization of the acyl hydrazone moiety. J. Med. Chem., 2015, 58(11), 4678-4692.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00223] [PMID: 25985283]
[156]
Zhang, J.L.; Liu, Y.; Yang, H.; Zhang, H.Q.; Tian, X.X.; Fang, W.G. ATP-P2Y2-β-catenin axis promotes cell invasion in breast cancer cells. Cancer Sci., 2017, 108(7), 1318-1327.
[http://dx.doi.org/10.1111/cas.13273] [PMID: 28474758]
[157]
Ji, L.; Qian, W.; Gui, L.; Ji, Z.; Yin, P.; Lin, G.N.; Wang, Y.; Ma, B.; Gao, W.Q. Blockade of β-Catenin–induced CCL28 suppresses gastric cancer progression viainhibition of treg cell infiltration. Cancer Res., 2020, 80(10), 2004-2016.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-3074] [PMID: 32156780]
[158]
Trujano-Camacho, S.; Cantú-de León, D.; Delgado-Waldo, I.; Coronel-Hernández, J.; Millan-Catalan, O.; Hernández-Sotelo, D.; López-Camarillo, C.; Pérez-Plasencia, C.; Campos-Parra, A.D. Inhibition of wnt-β-catenin signaling by ICRT14 drug depends of post-transcriptional regulation by hotair in human cervical cancer hela cells. Front. Oncol., 2021, 11, 29228.
[http://dx.doi.org/10.3389/fonc.2021.729228] [PMID: 34778043]
[159]
Jang, G.B.; Hong, I.S.; Kim, R.J.; Lee, S.Y.; Park, S.J.; Lee, E.S.; Park, J.H.; Yun, C.H.; Chung, J.U.; Lee, K.J.; Lee, H.Y.; Nam, J.S. Wnt/β-catenin small-molecule inhibitor CWP232228 preferentially inhibits the growth of breast cancer stem-like cells. Cancer Res., 2015, 75(8), 1691-1702.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-2041] [PMID: 25660951]
[160]
Kim, J.Y.; Lee, H.Y.; Park, K.K.; Choi, Y.K.; Nam, J.S.; Hong, I.S. CWP232228 targets liver cancer stem cells through Wnt/β-catenin signaling: A novel therapeutic approach for liver cancer treatment. Oncotarget, 2016, 7(15), 20395-20409.
[http://dx.doi.org/10.18632/oncotarget.7954] [PMID: 26967248]
[161]
Fang, L.; Zhu, Q.; Neuenschwander, M.; Specker, E.; Wulf-Goldenberg, A.; Weis, W.I.; von Kries, J.P.; Birchmeier, W. A small-molecule antagonist of the β-catenin/tcf4 interaction blocks the self-renewal of cancer stem cells and suppresses tumorigenesis. Cancer Res., 2016, 76(4), 891-901.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1519] [PMID: 26645562]
[162]
Deshmukh, V.; Hu, H.; Barroga, C.; Bossard, C.; Kc, S.; Dellamary, L.; Stewart, J.; Chiu, K.; Ibanez, M.; Pedraza, M.; Seo, T.; Do, L.; Cho, S.; Cahiwat, J.; Tam, B.; Tambiah, J.R.S.; Hood, J.; Lane, N.E.; Yazici, Y. A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee. Osteoarthritis Cartilage, 2018, 26(1), 18-27.
[http://dx.doi.org/10.1016/j.joca.2017.08.015] [PMID: 28888902]
[163]
Moroney, M.R.; Woodruff, E.; Qamar, L.; Bradford, A.P.; Wolsky, R.; Bitler, B.G.; Corr, B.R. Inhibiting Wnt/beta‐catenin in CTNNB1 ‐mutated endometrial cancer. Mol. Carcinog., 2021, 60(8), 511-523.
[http://dx.doi.org/10.1002/mc.23308] [PMID: 34038589]
[164]
Emami, K.H.; Nguyen, C.; Ma, H.; Kim, D.H.; Jeong, K.W.; Eguchi, M.; Moon, R.T.; Teo, J.L.; Kim, H.Y.; Moon, S.H.; Ha, J.R.; Kahn, M. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription. Proc. Natl. Acad. Sci., 2004, 101(34), 12682-12687.
[http://dx.doi.org/10.1073/pnas.0404875101] [PMID: 15314234]
[165]
Higuchi, Y.; Nguyen, C.; Yasuda, S.Y.; McMillan, M.; Hasegawa, K.; Kahn, M. Specific direct small molecule p300/β-catenin antagonists maintain stem cell potency. Curr. Mol. Pharmacol., 2016, 9(3), 272-279.
[http://dx.doi.org/10.2174/1874467208666150526155146] [PMID: 26008738]
[166]
Hao, J.; Ao, A.; Zhou, L.; Murphy, C.K.; Frist, A.Y.; Keel, J.J.; Thorne, C.A.; Kim, K.; Lee, E.; Hong, C.C. Selective small molecule targeting β-catenin function discovered by in vivo chemical genetic screen. Cell Rep., 2013, 4(5), 898-904.
[http://dx.doi.org/10.1016/j.celrep.2013.07.047] [PMID: 24012757]
[167]
Kahn, M. Taking the road less traveled – the therapeutic potential of CBP/β-catenin antagonists. Expert Opin. Ther. Targets, 2021, 25(9), 701-719.
[http://dx.doi.org/10.1080/14728222.2021.1992386] [PMID: 34633266]
[168]
Vallée, A.; Guillevin, R.; Vallée, J.N. Vasculogenesis and angiogenesis initiation under normoxic conditions through Wnt/β-catenin pathway in gliomas. Rev. Neurosci., 2017, 29(1), 71-91.
[http://dx.doi.org/10.1515/revneuro-2017-0032] [PMID: 28822229]
[169]
Zhang, X.; Gaspard, J.P.; Chung, D.C. Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in colonic neoplasia. Cancer Res., 2001, 61(16), 6050-6054.
[PMID: 11507052]
[170]
Easwaran, V.; Lee, S.H.; Inge, L.; Guo, L.; Goldbeck, C.; Garrett, E.; Wiesmann, M.; Garcia, P.D.; Fuller, J.H.; Chan, V.; Randazzo, F.; Gundel, R.; Warren, R.S.; Escobedo, J.; Aukerman, S.L.; Taylor, R.N.; Fantl, W.J. beta-Catenin regulates vascular endothelial growth factor expression in colon cancer. Cancer Res., 2003, 63(12), 3145-3153.
[PMID: 12810642]
[171]
Hanai, J.; Gloy, J.; Karumanchi, S.A.; Kale, S.; Tang, J.; Hu, G.; Chan, B.; Ramchandran, R.; Jha, V.; Sukhatme, V.P.; Sokol, S. Endostatin is a potential inhibitor of Wnt signaling. J. Cell Biol., 2002, 158(3), 529-539.
[http://dx.doi.org/10.1083/jcb.200203064] [PMID: 12147676]
[172]
Wu, T.; Duan, X.; Hu, T.; Mu, X.; Jiang, G.; Cui, S. Effect of endostatin on Wnt pathway of stem-like cells in bladder cancer in tumor microenvironment. Mol. Biol. Rep., 2020, 47(5), 3937-3948.
[http://dx.doi.org/10.1007/s11033-020-05487-3] [PMID: 32388699]
[173]
Park, C.H.; Hahm, E.R.; Park, S.; Kim, H.K.; Yang, C.H. The inhibitory mechanism of curcumin and its derivative against β-catenin/Tcf signaling. FEBS Lett., 2005, 579(13), 2965-2971.
[http://dx.doi.org/10.1016/j.febslet.2005.04.013] [PMID: 15893313]
[174]
Lu, Y.; Wei, C.; Xi, Z. Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/β-catenin pathway. in vitro Cell. Dev. Biol. Anim., 2014, 50(9), 840-850.
[http://dx.doi.org/10.1007/s11626-014-9779-5] [PMID: 24938356]
[175]
Wang, J.Y.; Wang, X.; Wang, X.J.; Zheng, B.Z.; Wang, Y.; Wang, X.; Liang, B. Curcumin inhibits the growth via Wnt/β-catenin pathway in non-small-cell lung cancer cells. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(21), 7492-7499.
[PMID: 30468498]
[176]
Ghasemi, F.; Shafiee, M.; Banikazemi, Z.; Pourhanifeh, M.H.; Khanbabaei, H.; Shamshirian, A.; Amiri Moghadam, S. ArefNezhad, R.; Sahebkar, A.; Avan, A.; Mirzaei, H. Curcumin inhibits NF-kB and Wnt/β-catenin pathways in cervical cancer cells. Pathol. Res. Pract., 2019, 215(10), 52556.
[http://dx.doi.org/10.1016/j.prp.2019.152556] [PMID: 31358480]
[177]
Yen, H.Y.; Tsao, C.W.; Lin, Y.W.; Kuo, C.C.; Tsao, C.H.; Liu, C.Y. Regulation of carcinogenesis and modulation through Wnt/β-catenin signaling by curcumin in an ovarian cancer cell line. Sci. Rep., 2019, 9(1), 17267.
[http://dx.doi.org/10.1038/s41598-019-53509-3] [PMID: 31754130]
[178]
Zoi, V.; Galani, V.; Lianos, G.D.; Voulgaris, S.; Kyritsis, A.P.; Alexiou, G.A. The role of curcumin in cancer treatment. Biomedicines, 2021, 9(9), 1086.
[http://dx.doi.org/10.3390/biomedicines9091086] [PMID: 34572272]
[179]
Zhang, B.; Abreu, J.G.; Zhou, K.; Chen, Y.; Hu, Y.; Zhou, T.; He, X.; Ma, J. Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family. Proc. Natl. Acad. Sci. USA, 2010, 107(15), 6900-6905.
[http://dx.doi.org/10.1073/pnas.0906764107] [PMID: 20351274]
[180]
Liu, X.; Lin, Z.; Zhou, T.; Zong, R.; He, H.; Liu, Z.; Ma, J.; Liu, Z.; Zhou, Y. Anti-angiogenic and anti-inflammatory effects of SERPINA3K on corneal injury. PLoS One, 2011, 6(1), e16712.
[http://dx.doi.org/10.1371/journal.pone.0016712] [PMID: 21304961]
[181]
Cui, J.; Jiang, W.; Wang, S.; Wang, L.; Xie, K. Role of Wnt/β-catenin signaling in drug resistance of pancreatic cancer. Curr. Pharm. Des., 2012, 18(17), 2464-2471.
[http://dx.doi.org/10.2174/13816128112092464] [PMID: 22372504]
[182]
Perry, J.M.; Tao, F.; Roy, A.; Lin, T.; He, X.C.; Chen, S.; Lu, X.; Nemechek, J.; Ruan, L.; Yu, X.; Dukes, D.; Moran, A.; Pace, J.; Schroeder, K.; Zhao, M.; Venkatraman, A.; Qian, P.; Li, Z.; Hembree, M.; Paulson, A.; He, Z.; Xu, D.; Tran, T.H.; Deshmukh, P.; Nguyen, C.T.; Kasi, R.M.; Ryan, R.; Broward, M.; Ding, S.; Guest, E.; August, K.; Gamis, A.S.; Godwin, A.; Sittampalam, G.S.; Weir, S.J.; Li, L. Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells. Nat. Cell Biol., 2020, 22(6), 689-700.
[http://dx.doi.org/10.1038/s41556-020-0507-y] [PMID: 32313104]
[183]
Vilchez, V.; Turcios, L.; Marti, F.; Gedaly, R. Targeting Wnt/β-catenin pathway in hepatocellular carcinoma treatment. World J. Gastroenterol., 2016, 22(2), 823-832.
[http://dx.doi.org/10.3748/wjg.v22.i2.823] [PMID: 26811628]
[184]
Leung, H.W.; Leung, C.O.N.; Lau, E.Y.; Chung, K.P.S.; Mok, E.H.; Lei, M.M.L.; Leung, R.W.H.; Tong, M.; Keng, V.W.; Ma, C.; Zhao, Q.; Ng, I.O.L.; Ma, S.; Lee, T.K. EPHB2 activates β-catenin to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma. Cancer Res., 2021, 81(12), 3229-3240.
[http://dx.doi.org/10.1158/0008-5472.CAN-21-0184] [PMID: 33903122]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy