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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Review Article

Wnt-β-catenin Signaling Pathway, the Achilles' Heels of Cancer Multidrug Resistance

Author(s): Morteza Ghandadi*, Reza Valadan, Hamidreza Mohammadi, Javad Akhtari, Shabanali Khodashenas and Sorour Ashari

Volume 25, Issue 39, 2019

Page: [4192 - 4207] Pages: 16

DOI: 10.2174/1381612825666191112142943

Price: $65


Background: Most of the anticancer chemotherapies are hampered via the development of multidrug resistance (MDR), which is the resistance of tumor cells against cytotoxic effects of multiple chemotherapeutic agents. Overexpression and/or over-activation of ATP-dependent drug efflux transporters is a key mechanism underlying MDR development. Moreover, enhancement of drug metabolism, changes in drug targets and aberrant activation of the main signaling pathways, including Wnt, Akt and NF-κB are also responsible for MDR.

Methods: In this study, we have reviewed the roles of Wnt signaling in MDR as well as its potential therapeutic significance. Pubmed and Scopus have been searched using Wnt, β-catenin, cancer, MDR and multidrug resistance as keywords. The last search was done in March 2019. Manuscripts investigating the roles of Wnt signaling in MDR or studying the modulation of MDR through the inhibition of Wnt signaling have been involved in the study. The main focus of the manuscript is regulation of MDR related transporters by canonical Wnt signaling pathway.

Result and conclusion: Wnt signaling has been involved in several pathophysiological states, including carcinogenesis and embryonic development. Wnt signaling is linked to various aspects of MDR including P-glycoprotein and multidrug resistance protein 1 regulation through its canonical pathways. Aberrant activation of Wnt/β- catenin signaling leads to the induction of cancer MDR mainly through the overexpression and/or over-activation of MDR related transporters. Accordingly, Wnt/β-catenin signaling can be a potential target for modulating cancer MDR.

Keywords: Wnt-β-catenin, cancer, multidrug resistance, cancer stem cell, miRNA, embryogenesis, chemotherapeutic.

Nikolaou M, Pavlopoulou A, Georgakilas AG, Kyrodimos E. The challenge of drug resistance in cancer treatment: a current overview. Clin Exp Metastasis 2018; 35(4): 309-18.
[] [PMID: 29799080]
Ji X, Lu Y, Tian H, Meng X, Wei M, Cho WC. Chemoresistance mechanisms of breast cancer and their countermeasures. Biomed Pharmacother 2019; 114108800
[] [PMID: 30921705]
Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: A brief review. Adv Pharm Bull 2017; 7(3): 339-48.
[] [PMID: 29071215]
Li W, Zhang H, Assaraf YG, et al. Overcoming ABC transporter-mediated multidrug resistance: molecular mechanisms and novel therapeutic drug strategies. Drug Resist Updat 2016; 27: 14-29.
[] [PMID: 27449595]
Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer 2018; 18(7): 452-64.
[] [PMID: 29643473]
Nanayakkara AK, Follit CA, Chen G, Williams NS, Vogel PD, Wise JG. Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells. Sci Rep 2018; 8(1): 967-7.
[] [PMID: 29343829]
Cascorbi I. P-glycoprotein: tissue distribution, substrates, and functional consequences of genetic variations. Handb Exp Pharmacol 2011; (201): 261-83.
[] [PMID: 21103972]
Waghray D, Zhang Q. Inhibit or evade multidrug resistance P-glycoprotein in cancer treatment. J Med Chem 2018; 61(12): 5108-21.
[] [PMID: 29251920]
Binkhathlan Z, Lavasanifar A. P-glycoprotein inhibition as a therapeutic approach for overcoming multidrug resistance in cancer: current status and future perspectives. Curr Cancer Drug Targets 2013; 13(3): 326-46.
[] [PMID: 23369096]
Ghandadi M, Behravan J, Abnous K, Ehtesham Gharaee M, Mosaffa F. TNF-α exerts cytotoxic effects on multidrug resistant breast cancer MCF-7/MX cells via a non-apoptotic death pathway. Cytokine 2017; 97: 167-74.
[] [PMID: 28651126]
Kartal-Yandim M, Adan-Gokbulut A, Baran Y. Molecular mechanisms of drug resistance and its reversal in cancer. Crit Rev Biotechnol 2016; 36(4): 716-26.
[PMID: 25757878]
Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 2017; 169(6): 985-99.
[] [PMID: 28575679]
Niehrs C, Acebron SP. Mitotic and mitogenic Wnt signalling. EMBO J 2012; 31(12): 2705-13.
[] [PMID: 22617425]
Loh KM, van Amerongen R, Nusse R. Generating cellular diversity and spatial form: Wnt signaling and the evolution of multicellular animals. Dev Cell 2016; 38(6): 643-55.
[] [PMID: 27676437]
Schneider J, Arraf AA, Grinstein M, Yelin R, Schultheiss TM. Wnt signaling orients the proximal-distal axis of chick kidney nephrons. Development 2015; 142(15): 2686-95.
[] [PMID: 26116665]
Sawa H. Chapter Three - Control of Cell Polarity and Asymmetric Division in C. elegans In: Yang Y, Ed., Current Topics in Developmental Biology. Academic Press, 2012; pp. 55-76.
Moon RT, Bowerman B, Boutros M, Perrimon N. The promise and perils of Wnt signaling through beta-catenin. Science 2002; 296(5573): 1644-6.
[] [PMID: 12040179]
MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 2009; 17(1): 9-26.
[] [PMID: 19619488]
Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: update on effectors and inhibitors. Cancer Treat Rev 2018; 62: 50-60.
[] [PMID: 29169144]
Thévenod F, Chakraborty PK. The role of Wnt/beta-catenin signaling in renal carcinogenesis: lessons from cadmium toxicity studies. Curr Mol Med 2010; 10(4): 387-404.
[] [PMID: 20455852]
Komiya Y, Habas R. Wnt signal transduction pathways. Organogenesis 2008; 4(2): 68-75.
[] [PMID: 19279717]
Schatoff EM, Leach BI, Dow LE. Wnt signaling and colorectal cancer. Curr Colorectal Cancer Rep 2017; 13(2): 101-10.
[] [PMID: 28413363]
Giannakis M, Hodis E, Jasmine Mu X, et al. RNF43 is frequently mutated in colorectal and endometrial cancers. Nat Genet 2014; 46(12): 1264-6.
[] [PMID: 25344691]
Khramtsov AI, Khramtsova GF, Tretiakova M, Huo D, Olopade OI, Goss KH. Wnt/beta-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome. Am J Pathol 2010; 176(6): 2911-20.
[] [PMID: 20395444]
Schade B, Lesurf R, Sanguin-Gendreau V, et al. β-Catenin signaling is a critical event in ErbB2-mediated mammary tumor progression. Cancer Res 2013; 73(14): 4474-87.
[] [PMID: 23720052]
Teng Y, Wang X, Wang Y, Ma D. Wnt/beta-catenin signaling regulates cancer stem cells in lung cancer A549 cells. Biochem Biophys Res Commun 2010; 392(3): 373-9.
[] [PMID: 20074550]
Lento W, Congdon K, Voermans C, Kritzik M, Reya T. Wnt signaling in normal and malignant hematopoiesis. Cold Spring Harb Perspect Biol 2013; 5(2): 5.
[] [PMID: 23378582]
Yeung J, Esposito MT, Gandillet A, et al. β-Catenin mediates the establishment and drug resistance of MLL leukemic stem cells. Cancer Cell 2010; 18(6): 606-18.
[] [PMID: 21156284]
Lane SW, Wang YJ, Lo Celso C, et al. Differential niche and Wnt requirements during acute myeloid leukemia progression. Blood 2011; 118(10): 2849-56.
[] [PMID: 21765021]
Müller-Tidow C, Steffen B, Cauvet T, et al. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol Cell Biol 2004; 24(7): 2890-904.
[] [PMID: 15024077]
Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene 2017; 36(11): 1461-73.
[] [PMID: 27617575]
Kageshita T, Hamby CV, Ishihara T, Matsumoto K, Saida T, Ono T. Loss of beta-catenin expression associated with disease progression in malignant melanoma. Br J Dermatol 2001; 145(2): 210-6.
[] [PMID: 11531781]
Bachmann IM, Straume O, Puntervoll HE, Kalvenes MB, Akslen LA. Importance of P-cadherin, beta-catenin, and Wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma. Clin Cancer Res 2005; 11(24 Pt 1): 8606-14.
[] [PMID: 16361544]
Chien AJ, Moore EC, Lonsdorf AS, et al. Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proc Natl Acad Sci USA 2009; 106(4): 1193-8.
[] [PMID: 19144919]
Biechele TL, Kulikauskas RM, Toroni RA, et al. Wnt/β-catenin signaling and AXIN1 regulate apoptosis triggered by inhibition of the mutant kinase BRAFV600E in human melanoma. Sci Signal 2012; 5(206): ra3.
[] [PMID: 22234612]
Damsky WE, Curley DP, Santhanakrishnan M, et al. β-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas. Cancer Cell 2011; 20(6): 741-54.
[] [PMID: 22172720]
Miyamoto DT, Zheng Y, Wittner BS, et al. RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 2015; 349(6254): 1351-6.
[] [PMID: 26383955]
O’Connell MP, Marchbank K, Webster MR, et al. Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2. Cancer Discov 2013; 3(12): 1378-93.
[] [PMID: 24104062]
Anastas JN, Kulikauskas RM, Tamir T, et al. WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors. J Clin Invest 2014; 124(7): 2877-90.
[] [PMID: 24865425]
El-Sahli S, Xie Y, Wang L, Liu S. Wnt signaling in cancer metabolism and immunity. Cancers (Basel) 2019; 11(7): 11.
[] [PMID: 31261718]
Kania KD, Wijesuriya HC, Hladky SB, Barrand MA. Beta amyloid effects on expression of multidrug efflux transporters in brain endothelial cells. Brain Res 2011; 1418: 1-11.
[] [PMID: 21920506]
Corrêa S, Binato R, Du Rocher B, Castelo-Branco MT, Pizzatti L, Abdelhay E. Wnt/β-catenin pathway regulates ABCB1 transcription in chronic myeloid leukemia. BMC Cancer 2012; 12: 303.
[] [PMID: 22823957]
Stein U, Fleuter C, Siegel F, et al. Impact of mutant β-catenin on ABCB1 expression and therapy response in colon cancer cells. Br J Cancer 2012; 106(8): 1395-405.
[] [PMID: 22460269]
Li L, Yang D, Cui D, et al. Quantitative proteomics analysis of the role of tetraspanin-8 in the drug resistance of gastric cancer. Int J Oncol 2018; 52(2): 473-84.
[PMID: 29345284]
Gonzalez-Exposito R, Semiannikova M, Griffiths B, et al. CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids. J Immunother Cancer 2019; 7(1): 101.
[] [PMID: 30982469]
Kim HJ, Moon SJ, Kim S-H, Heo K, Kim JH. DBC1 regulates Wnt/β-catenin-mediated expression of MACC1, a key regulator of cancer progression, in colon cancer. Cell Death Dis 2018; 9(8): 831.
[] [PMID: 30082743]
Zhang K, Li M, Huang H, et al. Dishevelled1-3 contribute to multidrug resistance in colorectal cancer via activating Wnt/β-catenin signaling. Oncotarget 2017; 8(70): 115803-16.
[] [PMID: 29383202]
Huang GL, Song W, Zhou P, et al. Oncogenic retinoic acid receptor γ knockdown reverses multi-drug resistance of human colorectal cancer via Wnt/β-catenin pathway. Cell Cycle 2017; 16(7): 685-92.
[] [PMID: 28272990]
Wang K, Chen D, Qian Z, Cui D, Gao L, Lou M. Hedgehog/Gli1 signaling pathway regulates MGMT expression and chemoresistance to temozolomide in human glioblastoma. Cancer Cell Int 2017; 17: 117-7.
[] [PMID: 29225516]
Wickström M, Dyberg C, Milosevic J, et al. Wnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance. Nat Commun 2015; 6: 8904.
[] [PMID: 26603103]
Li Y, Ma C, Shi X, et al. Effect of nitric oxide synthase on multiple drug resistance is related to Wnt signaling in non-small cell lung cancer. Oncol Rep 2014; 32(4): 1703-8.
[] [PMID: 25070480]
Xie C, Pan Y, Hao F, et al. C-Myc participates in β-catenin-mediated drug resistance in A549/DDP lung adenocarcinoma cells. APMIS 2014; 122(12): 1251-8.
[] [PMID: 25131138]
Bjorklund CC, Ma W, Wang ZQ, et al. Evidence of a role for activation of Wnt/beta-catenin signaling in the resistance of plasma cells to lenalidomide. J Biol Chem 2011; 286(13): 11009-20.
[] [PMID: 21189262]
Bjorklund CC, Baladandayuthapani V, Lin HY, et al. Evidence of a role for CD44 and cell adhesion in mediating resistance to lenalidomide in multiple myeloma: therapeutic implications. Leukemia 2014; 28(2): 373-83.
[] [PMID: 23760401]
Yin L, Tagde A, Gali R, et al. MUC1-C is a target in lenalidomide resistant multiple myeloma. Br J Haematol 2017; 178(6): 914-26.
[] [PMID: 28643330]
Liang Y, Li X, He X, et al. Polyphyllin I induces cell cycle arrest and apoptosis in human myeloma cells via modulating β-catenin signaling pathway. Eur J Haematol 2016; 97(4): 371-8.
[] [PMID: 26821882]
Zhao JJ, Lin J, Zhu D, et al. miR-30-5p functions as a tumor suppressor and novel therapeutic tool by targeting the oncogenic Wnt/β-catenin/BCL9 pathway. Cancer Res 2014; 74(6): 1801-13.
[] [PMID: 24599134]
Zhang H, Zhang X, Wu X, et al. Interference of Frizzled 1 (FZD1) reverses multidrug resistance in breast cancer cells through the Wnt/β-catenin pathway. Cancer Lett 2012; 323(1): 106-13.
[] [PMID: 22484497]
Zhang ZM, Wu JF, Luo QC, et al. Pygo2 activates MDR1 expression and mediates chemoresistance in breast cancer via the Wnt/β-catenin pathway. Oncogene 2016; 35(36): 4787-97.
[] [PMID: 26876203]
Rahmani F, Amerizadeh F, Hassanian SM, et al. PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin-induced cell growth via the Wnt pathway. J Cell Physiol 2019; 234(8): 14123-32.
[] [PMID: 30633353]
Zhang H, Gu H, Li L, Ren Y, Zhang L. EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway. Tumour Biol 2016; 37(5): 5919-23.
[] [PMID: 26592252]
Wang YH, Imai Y, Shiseki M, Tanaka J, Motoji T. Knockdown of the Wnt receptor Frizzled-1 (FZD1) reduces MDR1/P-glycoprotein expression in multidrug resistant leukemic cells and inhibits leukemic cell proliferation. Leuk Res 2018; 67: 99-108.
[] [PMID: 29482174]
Shen DY, Zhang W, Zeng X, Liu CQ. Inhibition of Wnt/β-catenin signaling downregulates P-glycoprotein and reverses multi-drug resistance of cholangiocarcinoma. Cancer Sci 2013; 104(10): 1303-8.
[] [PMID: 23822562]
Wang W, Zhong W, Yuan J, et al. Involvement of Wnt/β-catenin signaling in the mesenchymal stem cells promote metastatic growth and chemoresistance of cholangiocarcinoma. Oncotarget 2015; 6(39): 42276-89.
[] [PMID: 26474277]
Franqui-Machin R, Wendlandt EB, Janz S, Zhan F, Tricot G. Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction? Oncotarget 2015; 6(38): 40496-506.
[] [PMID: 26415231]
Prieto-Vila M, Takahashi R-U, Usuba W, Kohama I, Ochiya T. Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci 2017; 18(12): 2574.
[] [PMID: 29194401]
Phi LTH, Sari IN, Yang Y-G, et al. Cancer Stem Cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int 2018; 2018: 5416923-3.
[] [PMID: 29681949]
Cai C, Zhu X. The Wnt/β-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer. Mol Med Rep 2012; 5(5): 1191-6.
[PMID: 22367735]
Yang Y, Shi J, Gu Z, et al. Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple myeloma. Cancer Res 2015; 75(3): 594-604.
[] [PMID: 25589346]
Oishi N, Yamashita T, Kaneko S. Molecular biology of liver cancer stem cells. Liver Cancer 2014; 3(2): 71-84.
[] [PMID: 24944998]
Mohammed MK, Shao C, Wang J, et al. Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance. Genes Dis 2016; 3(1): 11-40.
[] [PMID: 27077077]
de Sousa E, Melo F, Vermeulen L, Vermeulen L. Wnt signaling in cancer stem cell biology. Cancers (Basel) 2016; 8(7): 60.
[] [PMID: 27355964]
Chen MS, Woodward WA, Behbod F, et al. Wnt/beta-catenin mediates radiation resistance of Sca1+ progenitors in an immortalized mammary gland cell line. J Cell Sci 2007; 120(Pt 3): 468-77.
[] [PMID: 17227796]
Huang M, Chen C, Geng J, et al. Targeting KDM1A attenuates Wnt/β-catenin signaling pathway to eliminate sorafenib-resistant stem-like cells in hepatocellular carcinoma. Cancer Lett 2017; 398: 12-21.
[] [PMID: 28377178]
Hsieh CH, Chao KS, Liao HF, Chen YJ. Norcantharidin, derivative of cantharidin, for cancer stem cells. Evid Based Complement Alternat Med 2013; 2013838651
[] [PMID: 24073010]
Lin LC, Yeh CT, Kuo CC, et al. Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/β-catenin function. J Agric Food Chem 2012; 60(28): 7031-9.
[] [PMID: 22708678]
Ghandadi M, Sahebkar A. MicroRNA-34a and its target genes: key factors in cancer multidrug resistance. Curr Pharm Des 2016; 22(7): 933-9.
[] [PMID: 26648462]
Cheng C, Qin Y, Zhi Q, Wang J, Qin C. Knockdown of long noncoding RNA HOTAIR inhibits cisplatin resistance of gastric cancer cells through inhibiting the PI3K/Akt and Wnt/β-catenin signaling pathways by up-regulating miR-34a. Int J Biol Macromol 2018; 107(Pt B): 2620-9.
[] [PMID: 29080815]
Liu Z, Zhang H. LncRNA plasmacytoma variant translocation 1 is an oncogene in bladder urothelial carcinoma. Oncotarget 2017; 8(38): 64273-82.
[] [PMID: 28969069]
Ma Y, Yang Y, Wang F, et al. Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/β-catenin signalling pathway via suppression of activator protein 2α. Gut 2016; 65(9): 1494-504.
[] [PMID: 25994219]
Zhang H, Hu B, Wang Z, Zhang F, Wei H, Li L. miR-181c contributes to cisplatin resistance in non-small cell lung cancer cells by targeting Wnt inhibition factor 1. Cancer Chemother Pharmacol 2017; 80(5): 973-84.
[] [PMID: 28956120]
Liu A, Zhu J, Wu G, et al. Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma. Mol Cancer 2017; 16(1): 106-6.
[] [PMID: 28633632]
Ong J, Timens W, Rajendran V, et al. Target gene identification of TGF-β-induced miR-455-3p and miR-21-3p in lung fibroblasts. Eur Respir J 2017; 50PA1025
Dong L, Deng J, Sun ZM, et al. Interference with the β-catenin gene in gastric cancer induces changes to the miRNA expression profile. Tumour Biol 2015; 36(9): 6973-83.
[] [PMID: 25861021]
Cai J, Fang L, Huang Y, et al. Simultaneous overactivation of Wnt/β-catenin and TGFβ signalling by miR-128-3p confers chemoresistance-associated metastasis in NSCLC. Nat Commun 2017; 8: 15870.
[] [PMID: 28627514]
Li H-Y, Liang J-L, Kuo Y-L, et al. miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer. Breast Cancer Res 2017; 19(1): 133-3.
[] [PMID: 29258605]
Drago-Ferrante R, Pentimalli F, Carlisi D, et al. Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation. Oncotarget 2017; 8(17): 28939-58.
[] [PMID: 28423652]
Blagodatski A, Poteryaev D, Katanaev VL. Targeting the Wnt pathways for therapies. Mol Cell Ther 2014; 2: 28-8.
[] [PMID: 26056595]
Katoh M, Katoh M. Molecular genetics and targeted therapy of WNT-related human diseases (Review). Int J Mol Med 2017; 40(3): 587-606.
[] [PMID: 28731148]
Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell Biosci 2017; 7: 50.
[] [PMID: 29034071]
Solmaz S, Adan Gokbulut A, Cincin B, et al. Therapeutic potential of apigenin, a plant flavonoid, for imatinib-sensitive and resistant chronic myeloid leukemia cells. Nutr Cancer 2014; 66(4): 599-612.
[] [PMID: 24669768]
Saeed M, Kadioglu O, Khalid H, Sugimoto Y, Efferth T. Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking. J Nutr Biochem 2015; 26(1): 44-56.
[] [PMID: 25459885]
Zhu Y, Liu C, Nadiminty N, et al. Inhibition of ABCB1 expression overcomes acquired docetaxel resistance in prostate cancer. Mol Cancer Ther 2013; 12(9): 1829-36.
[] [PMID: 23861346]
Angelini A, Di Ilio C, Castellani ML, Conti P, Cuccurullo F. Modulation of multidrug resistance P-glycoprotein activity by flavonoids and honokiol in human doxorubicin- resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. J Biol Regul Homeost Agents 2010; 24(2): 197-205.
[PMID: 20487633]
Lin C-M, Chen H-H, Lin C-A, Wu H-C, Sheu JJ-C, Chen H-J. Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling. Sci Rep 2017; 7(1): 372-2.
[] [PMID: 28337019]
Xu M, Wang S, Song YU, Yao J, Huang K, Zhu X. Apigenin suppresses colorectal cancer cell proliferation, migration and invasion via inhibition of the Wnt/β-catenin signaling pathway. Oncol Lett 2016; 11(5): 3075-80.
[] [PMID: 27123066]
Liu X, Li L, Lv L, Chen D, Shen L, Xie Z. Apigenin inhibits the proliferation and invasion of osteosarcoma cells by suppressing the Wnt/β-catenin signaling pathway. Oncol Rep 2015; 34(2): 1035-41.
[] [PMID: 26035210]
Huang GL, Shen DY, Cai CF, Zhang QY, Ren HY, Chen QX. β-escin reverses multidrug resistance through inhibition of the GSK3β/β-catenin pathway in cholangiocarcinoma. World J Gastroenterol 2015; 21(4): 1148-57.
[] [PMID: 25632187]
Mohana S, Ganesan M, Rajendra Prasad N, Ananthakrishnan D, Velmurugan D. Flavonoids modulate multidrug resistance through wnt signaling in P-glycoprotein overexpressing cell lines. BMC Cancer 2018; 18(1): 1168.
[] [PMID: 30477461]
Hamdoun S, Fleischer E, Klinger A, Efferth T. Lawsone derivatives target the Wnt/β-catenin signaling pathway in multidrug-resistant acute lymphoblastic leukemia cells. Biochem Pharmacol 2017; 146: 63-73.
[] [PMID: 29061340]
Yakisich JS, Azad N, Kaushik V, O’Doherty GA, Iyer AK. Nigericin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides. Tumour Biol 2017; 39(3)1010428317694310
[] [PMID: 28351327]
Mimeault M, Batra SK. Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy. Chin Med 2011; 6: 31.
[] [PMID: 21859497]
Guo Q, Chen Y, Zhang B, Kang M, Xie Q, Wu Y. Potentiation of the effect of gemcitabine by emodin in pancreatic cancer is associated with survivin inhibition. Biochem Pharmacol 2009; 77(11): 1674-83.
[] [PMID: 19428321]
Chen Z, Huang C, Ma T, et al. Reversal effect of quercetin on multidrug resistance via FZD7/β-catenin pathway in hepatocellular carcinoma cells. Phytomedicine 2018; 43: 37-45.
[] [PMID: 29747752]
Miyazaki Y, Shibuya M, Sugawara H, Kawaguchi O, Hirsoe C. Salinomycin, a new polyether antibiotic. J Antibiot (Tokyo) 1974; 27(11): 814-21.
[] [PMID: 4452657]
Naujokat C, Steinhart R. Salinomycin as a drug for targeting human cancer stem cells. J Biomed Biotechnol 2012; 2012950658
[] [PMID: 23251084]
Fuchs D, Daniel V, Sadeghi M, Opelz G, Naujokat C. Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells. Biochem Biophys Res Commun 2010; 394(4): 1098-104.
[] [PMID: 20350531]
Mao J, Fan S, Ma W, et al. Roles of Wnt/β-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell Death Dis 2014; 5e1039
[] [PMID: 24481453]
Gong C, Yao H, Liu Q, et al. Markers of tumor-initiating cells predict chemoresistance in breast cancer. PLoS One 2010; 5(12)e15630
[] [PMID: 21187973]
Oak PS, Kopp F, Thakur C, et al. Combinatorial treatment of mammospheres with trastuzumab and salinomycin efficiently targets HER2-positive cancer cells and cancer stem cells. Int J Cancer 2012; 131(12): 2808-19.
[] [PMID: 22511343]
Zhang Y, Zhang H, Wang X, Wang J, Zhang X, Zhang Q. The eradication of breast cancer and cancer stem cells using octreotide modified paclitaxel active targeting micelles and salinomycin passive targeting micelles. Biomaterials 2012; 33(2): 679-91.
[] [PMID: 22019123]
Zhang GN, Liang Y, Zhou LJ, et al. Combination of salinomycin and gemcitabine eliminates pancreatic cancer cells. Cancer Lett 2011; 313(2): 137-44.
[] [PMID: 22030254]
Zhou Y, Liang C, Xue F, et al. Salinomycin decreases doxorubicin resistance in hepatocellular carcinoma cells by inhibiting the β-catenin/TCF complex association via FOXO3a activation. Oncotarget 2015; 6(12): 10350-65.
[] [PMID: 25871400]
Zou Z-Z, Nie P-P, Li Y-W, et al. Synergistic induction of apoptosis by salinomycin and gefitinib through lysosomal and mitochondrial dependent pathway overcomes gefitinib resistance in colorectal cancer. Oncotarget 2017; 8(14): 22414-32.
[] [PMID: 26461472]
Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C. Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells. Biochem Biophys Res Commun 2009; 390(3): 743-9.
[] [PMID: 19835841]
Lu D, Choi MY, Yu J, Castro JE, Kipps TJ, Carson DA. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci USA 2011; 108(32): 13253-7.
[] [PMID: 21788521]
Huczyński A, Janczak J, Antoszczak M, Wietrzyk J, Maj E, Brzezinski B. Antiproliferative activity of salinomycin and its derivatives. Bioorg Med Chem Lett 2012; 22(23): 7146-50.
[] [PMID: 23079523]
Hero T, Bühler H, Kouam PN, Priesch-Grzeszowiak B, Lateit T, Adamietz IA. The triple-negative breast cancer cell line MDA-MB 231 is specifically inhibited by the ionophore Salinomycin. Anticancer Res 2019; 39(6): 2821-7.
[] [PMID: 31177119]
Wang B, Zou Q, Sun M, et al. Reversion of trichostatin a resistance via inhibition of the Wnt signaling pathway in human pancreatic cancer cells. Oncol Rep 2014; 32(5): 2015-22.
[] [PMID: 25224651]
Wu X, Luo F, Li J, Zhong X, Liu K. Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway. Int J Oncol 2016; 48(4): 1333-40.
[] [PMID: 26820603]
Merino VF, Cho S, Liang X, et al. Inhibitors of STAT3, β-catenin, and IGF-1R sensitize mouse PIK3CA-mutant breast cancer to PI3K inhibitors. Mol Oncol 2017; 11(5): 552-66.
[] [PMID: 28296140]
Arqués O, Chicote I, Puig I, et al. Tankyrase inhibition blocks Wnt/β-Catenin pathway and reverts resistance to PI3K and AKT inhibitors in the treatment of colorectal cancer. Clin Cancer Res 2016; 22(3): 644-56.
[] [PMID: 26224873]
Szwed M, Kania KD, Jozwiak Z. Toxicity of doxorubicin-transferrin conjugate is connected to the modulation of Wnt/β-catenin pathway in human leukemia cells. Leuk Res 2015; 39(10): 1096-102.
[] [PMID: 26271413]
Miller-Kleinhenz J, Guo X, Qian W, et al. Dual-targeting Wnt and uPA receptors using peptide conjugated ultra-small nanoparticle drug carriers inhibited cancer stem-cell phenotype in chemo-resistant breast cancer. Biomaterials 2018; 152: 47-62.
[] [PMID: 29107218]
Saifo MS, Rempinski DR Jr, Rustum YM, Azrak RG. Targeting the oncogenic protein beta-catenin to enhance chemotherapy outcome against solid human cancers. Mol Cancer 2010; 9: 310.
[] [PMID: 21126356]
Savvidou I, Khong T, Cuddihy A, McLean C, Horrigan S, Spencer A. β-Catenin inhibitor BC2059 is efficacious as monotherapy or in combination with proteasome inhibitor bortezomib in multiple myeloma. Mol Cancer Ther 2017; 16(9): 1765-78.
[] [PMID: 28500235]
Pak S, Park S, Kim Y, et al. 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.
[] [PMID: 31387608]
An T, Gong Y, Li X, et al. USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth. Biochem Pharmacol 2017; 131: 29-39.
[] [PMID: 28216017]
Cruz P, Reyes F, Torres CG. Simvastatin modulates β-catenin/MDR1 expression on spheres derived from CF41.Mg canine mammary carcinoma cells. Pol J Vet Sci 2018; 21(1): 95-9.
[PMID: 29624022]
Zhang H, Jing X, Wu X, et al. Suppression of multidrug resistance by rosiglitazone treatment in human ovarian cancer cells through downregulation of FZD1 and MDR1 genes. Anticancer Drugs 2015; 26(7): 706-15.
[] [PMID: 26053275]
Zhang B, Yang Y, Shi X, et al. Proton pump inhibitor pantoprazole abrogates adriamycin-resistant gastric cancer cell invasiveness via suppression of Akt/GSK-β/β-catenin signaling and epithelial-mesenchymal transition. Cancer Lett 2015; 356(2 Pt B): 704-12.
[] [PMID: 25449432]
Chen M, Wang J, Lu J, et al. The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling. Biochemistry 2009; 48(43): 10267-74.
[] [PMID: 19772353]
Londoño-Joshi AI, Arend RC, Aristizabal L, et al. Effect of niclosamide on basal-like breast cancers. Mol Cancer Ther 2014; 13(4): 800-11.
[] [PMID: 24552774]
Zhou J, Jin B, Jin Y, Liu Y, Pan J. The antihelminthic drug niclosamide effectively inhibits the malignant phenotypes of uveal melanoma in vitro and in vivo. Theranostics 2017; 7(6): 1447-62.
[] [PMID: 28529629]
Arend RC, Londoño-Joshi AI, Gangrade A, et al. Niclosamide and its analogs are potent inhibitors of Wnt/β-catenin, mTOR and STAT3 signaling in ovarian cancer. Oncotarget 2016; 7(52): 86803-15.
[] [PMID: 27888804]
Yin L, Gao Y, Zhang X, et al. Niclosamide sensitizes triple-negative breast cancer cells to ionizing radiation in association with the inhibition of Wnt/β-catenin signaling. Oncotarget 2016; 7(27): 42126-38.
[] [PMID: 27363012]
Giraudet A-L, Cassier PA, Iwao-Fukukawa C, et al. A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients. BMC Cancer 2018; 18(1): 646-.
[] [PMID: 29884132]
Säfholm A, Tuomela J, Rosenkvist J, Dejmek J, Härkönen P, Andersson T. The Wnt-5a-derived hexapeptide Foxy-5 inhibits breast cancer metastasis in vivo by targeting cell motility. Clin Cancer Res 2008; 14(20): 6556-63.
[] [PMID: 18927296]
Kahn M. Can we safely target the WNT pathway? Nat Rev Drug Discov 2014; 13(7): 513-32.
[] [PMID: 24981364]
Bendell J, Eckhardt GS, Hochster HS, et al. Initial results from a phase 1a/b study of OMP-131R10, a first-in-class anti-RSPO3 antibody, in advanced solid tumors and previously treated metastatic colorectal cancer (CRC). Eur J Cancer 2016; 69: S29-30.
Jimeno A, Gordon M, Chugh R, et al. A first-in-human phase I anticancer study of the stem cell agent ipafricept (OMP-54F28), a decoy receptor for wnt ligands, in patients with advanced solid tumors. Clin Cancer Res 2017; 23(24): 7490-7.
[] [PMID: 28954784]
Liu J, Pan S, Hsieh MH, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci USA 2013; 110(50): 20224-9.
[] [PMID: 24277854]
Madan B, Ke Z, Harmston N, et al. Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene 2016; 35(17): 2197-207.
[] [PMID: 26257057]
Fang L, Zhu Q, Neuenschwander M, et al. 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.
[] [PMID: 26645562]
Ruan H, Zhan YY, Hou J, et al. Berberine binds RXRα to suppress β-catenin signaling in colon cancer cells. Oncogene 2017; 36(50): 6906-18.
[] [PMID: 28846104]

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