Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

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

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

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review

Author(s): Seyed H. Shahcheraghi, Venant Tchokonte-Nana, Marzieh Lotfi, Malihe Lotfi, Ahmad Ghorbani* and Hamid R. Sadeghnia*

Volume 26, Issue 15, 2020

Page: [1729 - 1741] Pages: 13

DOI: 10.2174/1381612826666200131100630

Price: $65

Abstract

Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

Keywords: Glioblastoma, cancer, molecular mechanisms, Wnt signaling pathway, PI3K/Akt/mTOR pathway, chemotherapy.

« Previous Next »
[1]
Bahmad HF, Mouhieddine TH, Chalhoub RM, et al. The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic target for glioblastoma and neuroblastoma. Oncotarget 2018; 9(71): 33549-61.
[http://dx.doi.org/10.18632/oncotarget.26088] [PMID: 30323898]
[2]
Shen X, Zhang J, Zhang X, Wang Y, Hu Y, Guo J. Retinoic acid-induced protein 14 (RAI14) promotes mTOR-mediated inflammation under inflammatory stress and chemical hypoxia in a U87 glioblastoma cell line. Cell Mol Neurobiol 2019; 39(2): 241-54.
[http://dx.doi.org/10.1007/s10571-018-0644-z] [PMID: 30554401]
[3]
Liu Z, Wang F, Zhou Z-W, et al. Alisertib induces G2/M arrest, apoptosis, and autophagy via PI3K/Akt/mTOR- and p38 MAPK-mediated pathways in human glioblastoma cells. Am J Transl Res 2017; 9(3): 845-73.
[PMID: 28386317]
[4]
Bai Z-L, Tay V, Guo S-Z, Ren J, Shu M-G. Silibinin induced human glioblastoma cell apoptosis concomitant with autophagy through simultaneous inhibition of mTOR and YAP. BioMed Res Int 2018; 2018
[http://dx.doi.org/10.1155/2018/6165192]
[5]
Li ZZ, Wang YL, Yu YH, Xing YL, Ji XF. Aclidinium bromide inhibits proliferation of osteosarcoma cells through regulation of PI3K/Akt pathway. Eur Rev Med Pharmacol Sci 2019; 23(1): 105-12.
[PMID: 30657552]
[6]
Dai Z, Wang L, Wang X, et al. Oxymatrine induces cell cycle arrest and apoptosis and suppresses the invasion of human glioblastoma cells through the EGFR/PI3K/Akt/mTOR signaling pathway and STAT3. Oncol Rep 2018; 40(2): 867-76.
[http://dx.doi.org/10.3892/or.2018.6512] [PMID: 29989652]
[7]
Shao M, He Z, Yin Z, et al. Xihuang pill induces apoptosis of human glioblastoma U-87 MG cells via targeting ROS-mediated Akt/mTOR/FOXO1 pathway. Evid Based Complement Alternat Med 2018; 2018
[8]
Louis DN, Perry A, Reifenberger G, et al. The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 2016; 131(6): 803-20.
[http://dx.doi.org/10.1007/s00401-016-1545-1] [PMID: 27157931]
[9]
Shahcheraghi SH, Zangui M, Lotfi M, et al. Therapeutic potential of curcumin in the treatment of glioblastoma multiforme. Curr Pharm Des 2019; 25(3): 333-42.
[http://dx.doi.org/10.2174/1381612825666190313123704] [PMID: 30864499]
[10]
Zhang J, Huang K, Shi Z, et al. High β-catenin/Tcf-4 activity confers glioma progression via direct regulation of AKT2 gene expression. Neuro-oncol 2011; 13(6): 600-9.
[http://dx.doi.org/10.1093/neuonc/nor034] [PMID: 21636708]
[11]
Mazurek A, Luo W, Krasnitz A, Hicks J, Powers RS, Stillman B. DDX5 regulates DNA replication and is required for cell proliferation in a subset of breast cancer cells. Cancer Discov 2012; 2(9): 812-25.
[http://dx.doi.org/10.1158/2159-8290.CD-12-0116] [PMID: 22750847]
[12]
Sarkar M, Khare V, Guturi KK, Das N, Ghosh MK. The DEAD box protein p68: a crucial regulator of AKT/FOXO3a signaling axis in oncogenesis. Oncogene 2015; 34(47): 5843-56.
[http://dx.doi.org/10.1038/onc.2015.42] [PMID: 25745998]
[13]
Tan SK, Jermakowicz A, Mookhtiar AK, Nemeroff CB, Schürer SC, Ayad NG. Drug repositioning in glioblastoma: a pathway perspective. Front Pharmacol 2018; 9: 218.
[http://dx.doi.org/10.3389/fphar.2018.00218] [PMID: 29615902]
[14]
Rossi M, Magnoni L, Miracco C, et al. β-catenin and Gli1 are prognostic markers in glioblastoma. Cancer Biol Ther 2011; 11(8): 753-61.
[http://dx.doi.org/10.4161/cbt.11.8.14894] [PMID: 21321483]
[15]
Furukawa K, Kumon Y, Harada H, et al. PTEN gene transfer suppresses the invasive potential of human malignant gliomas by regulating cell invasion-related molecules. Int J Oncol 2006; 29(1): 73-81.
[http://dx.doi.org/10.3892/ijo.29.1.73] [PMID: 16773187]
[16]
Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000; 103(2): 253-62.
[http://dx.doi.org/10.1016/S0092-8674(00)00117-3] [PMID: 11057898]
[17]
Neshat MS, Mellinghoff IK, Tran C, et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci USA 2001; 98(18): 10314-9.
[http://dx.doi.org/10.1073/pnas.171076798] [PMID: 11504908]
[18]
Geoerger B, Kerr K, Tang C-B, et al. Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy. Cancer Res 2001; 61(4): 1527-32.
[PMID: 11245461]
[19]
Chen Q, Weng HY, Tang XP, et al. ARL4C stabilized by AKT/mTOR pathway promotes the invasion of PTEN-deficient primary human glioblastoma. J Pathol 2019; 247(2): 266-78.
[http://dx.doi.org/10.1002/path.5189] [PMID: 30357833]
[20]
Zhang WB, Wang Z, Shu F, et al. Activation of AMP-activated protein kinase by temozolomide contributes to apoptosis in glioblastoma cells via p53 activation and mTORC1 inhibition. J Biol Chem 2010; 285(52): 40461-71.
[http://dx.doi.org/10.1074/jbc.M110.164046] [PMID: 20880848]
[21]
Bi Y, Li H, Yi D, et al. Cordycepin augments the chemosensitivity of human glioma cells to temozolomide by activating AMPK and inhibiting the AKT signaling pathway. Mol Pharm 2018; 15(11): 4912-25.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00551] [PMID: 30336060]
[22]
Gil del Alcazar CR, Hardebeck MC, Mukherjee B, et al. Inhibition of DNA double-strand break repair by the dual PI3K/mTOR inhibitor NVP-BEZ235 as a strategy for radiosensitization of glioblastoma. Clin Cancer Res 2014; 20(5): 1235-48.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-1607] [PMID: 24366691]
[23]
Nanta R, Shrivastava A, Sharma J, Shankar S, Srivastava RK. Inhibition of sonic hedgehog and PI3K/Akt/mTOR pathways cooperate in suppressing survival, self-renewal and tumorigenic potential of glioblastoma-initiating cells. Mol Cell Biochem 2018; 1-13.
[PMID: 30251117]
[24]
Chen ZX, Wallis K, Fell SM, et al. RNA helicase A is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma. Cancer Discov 2014; 4(4): 434-51.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0362] [PMID: 24469107]
[25]
Heerma van Voss MR, van Diest PJ, Raman V. Targeting RNA helicases in cancer: The translation trap. Biochim Biophys Acta Rev Cancer 2017; 1868(2): 510-20.
[http://dx.doi.org/10.1016/j.bbcan.2017.09.006] [PMID: 28965870]
[26]
Taniguchi K, Iwatsuki A, Sugito N, et al. Oncogene RNA helicase DDX6 promotes the process of c-Myc expression in gastric cancer cells. Mol Carcinog 2018; 57(5): 579-89.
[http://dx.doi.org/10.1002/mc.22781] [PMID: 29314290]
[27]
Wang H, Yu J, Wang X, Zhang Y. The RNA helicase DHX33 is required for cancer cell proliferation in human glioblastoma and confers resistance to PI3K/mTOR inhibition. Cell Signal 2019; 54: 170-8.
[http://dx.doi.org/10.1016/j.cellsig.2018.12.005] [PMID: 30552990]
[28]
Petővári G, Hujber Z, Krencz I, et al. Targeting cellular metabolism using rapamycin and/or doxycycline enhances anti-tumour effects in human glioma cells. Cancer Cell Int 2018; 18: 211.
[http://dx.doi.org/10.1186/s12935-018-0710-0] [PMID: 30574020]
[29]
Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012; 149(2): 274-93.
[http://dx.doi.org/10.1016/j.cell.2012.03.017] [PMID: 22500797]
[30]
Huang W, Ding X, Ye H, Wang J, Shao J, Huang T. Hypoxia enhances the migration and invasion of human glioblastoma U87 cells through PI3K/Akt/mTOR/HIF-1α pathway. Neuroreport 2018; 29(18): 1578-85.
[http://dx.doi.org/10.1097/WNR.0000000000001156] [PMID: 30371540]
[31]
Mattoo AR, Joun A, Jessup JM. Repurposing of mTOR complex inhibitors attenuates MCL-1 and sensitizes to PARP inhibition. Mol Cancer Res 2019; 17(1): 42-53.
[http://dx.doi.org/10.1158/1541-7786.MCR-18-0650] [PMID: 30201826]
[32]
Xia P, Xu X-Y. PI3K/Akt/mTOR signaling pathway in cancer stem cells: from basic research to clinical application. Am J Cancer Res 2015; 5(5): 1602-9.
[PMID: 26175931]
[33]
Sami A, Karsy M. Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma: novel therapeutic agents and advances in understanding. Tumour Biol 2013; 34(4): 1991-2002.
[http://dx.doi.org/10.1007/s13277-013-0800-5] [PMID: 23625692]
[34]
Douglas DA, Zhong H, Ro JY, et al. Novel mutations of epidermal growth factor receptor in localized prostate cancer. Front Biosci 2006; 11: 2518-25.
[http://dx.doi.org/10.2741/1986] [PMID: 16720329]
[35]
Chin L. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2013; 494: 506-6.
[36]
Jhanwar-Uniyal M, Jeevan D, Neil J, Shannon C, Albert L, Murali R. Deconstructing mTOR complexes in regulation of Glioblastoma Multiforme and its stem cells. Adv Biol Regul 2013; 53(2): 202-10.
[http://dx.doi.org/10.1016/j.jbior.2012.10.001] [PMID: 23231881]
[37]
Denysenko T, Annovazzi L, Cassoni P, Melcarne A, Mellai M, Schiffer D. WNT/β-catenin signaling pathway and downstream modulators in low-and high-grade glioma. Cancer Genomics Proteomics 2016; 13(1): 31-45.
[PMID: 26708597]
[38]
Rheinbay E, Suvà ML, Gillespie SM, et al. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Cell Rep 2013; 3(5): 1567-79.
[http://dx.doi.org/10.1016/j.celrep.2013.04.021] [PMID: 23707066]
[39]
Lee Y, Lee J-K, Ahn SH, Lee J, Nam D-H. WNT signaling in glioblastoma and therapeutic opportunities. Lab Invest 2016; 96(2): 137-50.
[http://dx.doi.org/10.1038/labinvest.2015.140] [PMID: 26641068]
[40]
Kim Y, Kim KH, Lee J, et al. Wnt activation is implicated in glioblastoma radioresistance. Lab Invest 2012; 92(3): 466-73.
[http://dx.doi.org/10.1038/labinvest.2011.161] [PMID: 22083670]
[41]
Yuan J, Zhang F, Hallahan D, et al. Reprogramming glioblastoma multiforme cells into neurons by protein kinase inhibitors. J Exp Clin Cancer Res 2018; 37(1): 181.
[http://dx.doi.org/10.1186/s13046-018-0857-5] [PMID: 30071868]
[42]
Mecca C, Giambanco I, Bruscoli S, et al. PP242 counteracts glioblastoma cell proliferation, migration, invasiveness and stemness properties by inhibiting mTORC2/AKT. Front Cell Neurosci 2018; 12: 99.
[http://dx.doi.org/10.3389/fncel.2018.00099] [PMID: 29692710]
[43]
Benavides-Serrato A, Lee J, Holmes B, et al. Correction: Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is cytotoxic in glioblastoma. PLoS One 2019; 14(2)e0212160
[http://dx.doi.org/10.1371/journal.pone.0212160] [PMID: 30726300]
[44]
Li ZY, Zhang C, Chen L, et al. Radicol, a novel trinorguaiane-type sesquiterpene, induces temozolomide-resistant glioma cell apoptosis via ER stress and Akt/mTOR pathway blockade. Phytother Res 2017; 31(5): 729-39.
[http://dx.doi.org/10.1002/ptr.5793] [PMID: 28240396]
[45]
Olmez I, Brenneman B, Xiao A, et al. Combined CDK4/6 and mTOR inhibition is synergistic against glioblastoma via multiple mechanisms. Clin Cancer Res 2017; 23(22): 6958-68.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0803] [PMID: 28814434]
[46]
Wang Q, Wang H, Jia Y, Ding H, Zhang L, Pan H. Luteolin reduces migration of human glioblastoma cell lines via inhibition of the p-IGF-1R/PI3K/AKT/mTOR signaling pathway. Oncol Lett 2017; 14(3): 3545-51.
[http://dx.doi.org/10.3892/ol.2017.6643] [PMID: 28927111]
[47]
Huang H, Song J, Liu Z, Pan L, Xu G. Autophagy activation promotes bevacizumab resistance in glioblastoma by suppressing Akt/mTOR signaling pathway. Oncol Lett 2018; 15(2): 1487-94.
[PMID: 29434840]
[48]
Agliano A, Balarajah G, Ciobota DM, et al. Pediatric and adult glioblastoma radiosensitization induced by PI3K/mTOR inhibition causes early metabolic alterations detected by nuclear magnetic resonance spectroscopy. Oncotarget 2017; 8(29): 47969-83.
[http://dx.doi.org/10.18632/oncotarget.18206] [PMID: 28624789]
[49]
Song Y, Chen Y, Li Y, et al. Metformin inhibits TGF-β1-induced epithelial-to-mesenchymal transition-like process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway. Oncotarget 2017; 9(6): 7023-35.
[PMID: 29467947]
[50]
NCT02430363. Evaluation of the treatment effectiveness of glioblastoma / gliosarcoma through the suppression of the pi3k/akt pathway in compared with MK-3475. Available at: https://clinicaltrials.gov/ct2/show/NCT02430363?term=Akt+inhibitors&cond=Glioblastoma&rank=1.In: ed.^eds.,2018.
[51]
NCT00897663 Improving the selection of patients with glioblastoma multiforme for treatment with epidermal growth factor receptor inhibitor therapies Available at:. https://clinicaltrials.gov/ct2/show/NCT00897663?term=Akt+inhibitors&cond=Glioblastoma&rank=2.In: ed.^eds.,2018.
[52]
Dong Z, Zhou L, Han N, Zhang M, Lyu X. Wnt/β-catenin pathway involvement in ionizing radiation-induced invasion of U87 glioblastoma cells. Strahlenther Onkol 2015; 191(8): 672-80.
[http://dx.doi.org/10.1007/s00066-015-0858-7] [PMID: 26072169]
[53]
Gao L, Chen B, Li J, et al. Wnt/β-catenin signaling pathway inhibits the proliferation and apoptosis of U87 glioma cells via different mechanisms. PLoS One 2017; 12(8)e0181346
[http://dx.doi.org/10.1371/journal.pone.0181346] [PMID: 28837560]
[54]
Jiang Y, Miao J, Wang D, et al. MAP30 promotes apoptosis of U251 and U87 cells by suppressing the LGR5 and Wnt/β-catenin signaling pathway, and enhancing Smac expression. Oncol Lett 2018; 15(4): 5833-40.
[http://dx.doi.org/10.3892/ol.2018.8073] [PMID: 29556310]
[55]
Qiang Z, Jun-Jie L, Hai W, et al. TPD52L2 impacts proliferation, invasiveness and apoptosis of glioblastoma cells via modulation of wnt/β-catenin/snail signaling. Carcinogenesis 2018; 39(2): 214-24.
[http://dx.doi.org/10.1093/carcin/bgx125] [PMID: 29106517]
[56]
Cui X, Sun D, Shen B, Wang X. MEG-3-mediated Wnt/β-catenin signaling pathway controls the inhibition of tunicamycin-mediated viability in glioblastoma. Oncol Lett 2018; 16(3): 2797-804.
[http://dx.doi.org/10.3892/ol.2018.9048] [PMID: 30127865]
[57]
Gonçalves CS, Vieira de Castro J, Pojo M, et al. WNT6 is a novel oncogenic prognostic biomarker in human glioblastoma. Theranostics 2018; 8(17): 4805-23.
[http://dx.doi.org/10.7150/thno.25025] [PMID: 30279739]
[58]
Nàger M, Sallán MC, Visa A, et al. Inhibition of WNT-CTNNB1 signaling upregulates SQSTM1 and sensitizes glioblastoma cells to autophagy blockers. Autophagy 2018; 14(4): 619-36.
[http://dx.doi.org/10.1080/15548627.2017.1423439] [PMID: 29313411]
[59]
Pu P, Zhang Z, Kang C, et al. Downregulation of Wnt2 and β-catenin by siRNA suppresses malignant glioma cell growth. Cancer Gene Ther 2009; 16(4): 351-61.
[http://dx.doi.org/10.1038/cgt.2008.78] [PMID: 18949017]
[60]
Binda E, Visioli A, Giani F, et al. Wnt5a drives an invasive phenotype in human glioblastoma stem-like cells. Cancer Res 2017; 77(4): 996-1007.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1693] [PMID: 28011620]
[61]
Adamo A, Fiore D, De Martino F, et al. RYK promotes the stemness of glioblastoma cells via the WNT/ β-catenin pathway. Oncotarget 2017; 8(8): 13476-87.
[http://dx.doi.org/10.18632/oncotarget.14564] [PMID: 28086236]
[62]
Kim Y, Hong M, Do I-G, Ha SY, Lee D, Suh Y-L. Wnt5a, Ryk and Ror2 expression in glioblastoma subgroups. Pathol Res Pract 2015; 211(12): 963-72.
[http://dx.doi.org/10.1016/j.prp.2015.10.001] [PMID: 26596412]
[63]
Cui D, Ren J, Shi J, et al. R132H mutation in IDH1 gene reduces proliferation, cell survival and invasion of human glioma by downregulating Wnt/β-catenin signaling. Int J Biochem Cell Biol 2016; 73: 72-81.
[http://dx.doi.org/10.1016/j.biocel.2016.02.007] [PMID: 26860959]
[64]
Chu C-W, Ko H-J, Chou C-H, et al. Thioridazine enhances P62-Mediated autophagy and apoptosis through Wnt/β-Catenin signaling pathway in glioma cells. Int J Mol Sci 2019; 20(3): 20.
[http://dx.doi.org/10.3390/ijms20030473] [PMID: 30678307]
[65]
Zuccarini M, Giuliani P, Ziberi S, et al. The role of Wnt signal in glioblastoma development and progression: a possible new pharmacological target for the therapy of this tumor. Genes (Basel) 2018; 9(2): 105.
[http://dx.doi.org/10.3390/genes9020105] [PMID: 29462960]
[66]
Lu C, Cui C, Liu B, et al. FERMT3 contributes to glioblastoma cell proliferation and chemoresistance to temozolomide through integrin mediated Wnt signaling. Neurosci Lett 2017; 657: 77-83.
[http://dx.doi.org/10.1016/j.neulet.2017.07.057] [PMID: 28778805]
[67]
Chen Q, Cai J, Wang Q, et al. Long noncoding RNA NEAT1, regulated by the EGFR pathway, contributes to glioblastoma progression through the WNT/β-catenin pathway by scaffolding EZH2. Clin Cancer Res 2018; 24(3): 684-95.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0605] [PMID: 29138341]
[68]
Suwala AK, Koch K, Rios DH, et al. Inhibition of Wnt/beta-catenin signaling downregulates expression of aldehyde dehydrogenase isoform 3A1 (ALDH3A1) to reduce resistance against temozolomide in glioblastoma in vitro. Oncotarget 2018; 9(32): 22703-16.
[http://dx.doi.org/10.18632/oncotarget.25210] [PMID: 29854309]
[69]
Kierulf-Vieira KS, Sandberg CJ, Grieg Z, Günther C-C, Langmoen IA, Vik-Mo EO. Wnt inhibition is dysregulated in gliomas and its re-establishment inhibits proliferation and tumor sphere formation. Exp Cell Res 2016; 340(1): 53-61.
[http://dx.doi.org/10.1016/j.yexcr.2015.12.010] [PMID: 26712519]
[70]
Tao H, Guo L, Chen L, et al. MSX1 inhibits cell migration and invasion through regulating the Wnt/β-catenin pathway in glioblastoma. Tumour Biol 2016; 37(1): 1097-104.
[http://dx.doi.org/10.1007/s13277-015-3892-2] [PMID: 26271668]
[71]
Mora MC, Bassa LM, Wong KE, Tirabassi MV, Arenas RB, Schneider SS. Rhodiola crenulata inhibits Wnt/β-catenin signaling in glioblastoma. J Surg Res 2015; 197(2): 247-55.
[http://dx.doi.org/10.1016/j.jss.2015.02.074] [PMID: 25998182]
[72]
Lan F, Pan Q, Yu H, Yue X. Sulforaphane enhances temozolomide-induced apoptosis because of down-regulation of miR-21 via Wnt/β-catenin signaling in glioblastoma. J Neurochem 2015; 134(5): 811-8.
[http://dx.doi.org/10.1111/jnc.13174] [PMID: 25991372]
[73]
Zhang W, Shen C, Li C, et al. miR-577 inhibits glioblastoma tumor growth via the Wnt signaling pathway. Mol Carcinog 2016; 55(5): 575-85.
[http://dx.doi.org/10.1002/mc.22304] [PMID: 25764520]
[74]
Guo M, Zhang X, Wang G, et al. miR-603 promotes glioma cell growth via Wnt/β-catenin pathway by inhibiting WIF1 and CTNNBIP1. Cancer Lett 2015; 360(1): 76-86.
[http://dx.doi.org/10.1016/j.canlet.2015.02.003] [PMID: 25681036]
[75]
Bhuvanalakshmi G, Gamit N, Patil M, et al. Stemness, pluripotentiality, and Wnt antagonism: sFRP4, a Wnt antagonist mediates pluripotency and stemness in glioblastoma. Cancers (Basel) 2018; 11(1): 25.
[http://dx.doi.org/10.3390/cancers11010025] [PMID: 30591679]
[76]
Kim S, Jho EH. Merlin, a regulator of Hippo signaling, regulates Wnt/β-catenin signaling. BMB Rep 2016; 49(7): 357-8.
[http://dx.doi.org/10.5483/BMBRep.2016.49.7.104] [PMID: 27345717]
[77]
Riva G, Cilibrasi C, Bazzoni R, et al. Valproic acid inhibits proliferation and reduces invasiveness in glioma stem cells through Wnt/β catenin signalling activation. Genes (Basel) 2018; 9(11): 522.
[http://dx.doi.org/10.3390/genes9110522] [PMID: 30373123]
[78]
Kouchi M, Shibayama Y, Ogawa D, Miyake K, Nishiyama A, Tamiya T. (Pro)renin receptor is crucial for glioma development via the Wnt/β-catenin signaling pathway. J Neurosurg 2017; 127(4): 819-28.
[http://dx.doi.org/10.3171/2016.9.JNS16431] [PMID: 28059652]
[79]
Liu X, Gao Q, Zhao N, et al. Sohlh1 suppresses glioblastoma cell proliferation, migration, and invasion by inhibition of Wnt/β-catenin signaling. Mol Carcinog 2018; 57(4): 494-502.
[http://dx.doi.org/10.1002/mc.22774] [PMID: 29240260]
[80]
Khan M, Muzumdar D, Shiras A. Attenuation of tumor suppressive function of FBXO16 ubiquitin ligase activates wnt signaling in glioblastoma. Neoplasia 2019; 21(1): 106-16.
[http://dx.doi.org/10.1016/j.neo.2018.11.005] [PMID: 30530053]
[81]
Matias D, Dubois LG, Pontes B, et al. GBM-derived Wnt3a induces M2-like phenotype in microglial cells through Wnt/β-catenin signaling. Mol Neurobiol 2019; 56(2): 1517-30.
[http://dx.doi.org/10.1007/s12035-018-1150-5] [PMID: 29948952]
[82]
Oikonomaki M, Bady P, Hegi ME. Ubiquitin Specific Peptidase 15 (USP15) suppresses glioblastoma cell growth via stabilization of HECTD1 E3 ligase attenuating WNT pathway activity. Oncotarget 2017; 8(66): 110490-502.
[http://dx.doi.org/10.18632/oncotarget.22798] [PMID: 29299163]
[83]
Cilibrasi C, Riva G, Romano G, et al. Resveratrol impairs glioma stem cells proliferation and motility by modulating the Wnt signaling pathway. PLoS One 2017; 12(1)e0169854
[http://dx.doi.org/10.1371/journal.pone.0169854] [PMID: 28081224]
[84]
Zhang C, Yang X, Fu C, Liu X. Combination with TMZ and miR-505 inhibits the development of glioblastoma by regulating the WNT7B/Wnt/β-catenin signaling pathway. Gene 2018; 672: 172-9.
[http://dx.doi.org/10.1016/j.gene.2018.06.030] [PMID: 29906532]

Rights & Permissions Print Cite
Article Metrics
163
8
World Health Day
© 2024 Bentham Science Publishers | Privacy Policy