GSK-3 as potential target for therapeutic intervention in cancer

Oncotarget - Tập 5 Số 10 - Trang 2881-2911 - 2014
James A. McCubrey1, Linda S. Steelman2, F. E. Bertrand3, Nicole D. Armstrong2, Melissa L. Sokolosky2, Steve L. Abrams2, Giuseppe Montalto4, Antonino B. D’Assoro5, Massimo Libra6, Ferdinando Nicoletti6, Roberta Maestro7, Jörg Bäsecke8,9, Dariusz Rakus10, Agnieszka Gizak10, Zoya N. Demidenko11, Lucio Cocco12, Alberto M. Martelli12, Melchiorre Cervello13
1Department of Microbiology & Immunology, Brody School of Medicine at East Carolina University Greenville, NC 27858, USA.
2Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
3Department of Oncology, Brody School of Medicine at East Carolina University Greenville, NC, USA
4Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy
5Department of Medical Oncology, Mayo Clinic Cancer Center, Rochester, MN, USA
6Department of Bio-Medical Sciences, University of Catania, Catania, Italy
7Experimental Oncology 1, CRO IRCCS, National Cancer Institute, Aviano, Pordenone, Italy
8Department of Medicine, University of Göttingen, Göttingen, Germany
9Sanct-Josef-Hospital Cloppenburg, Department of Hematology and Oncology, Cloppenburg, Germany
10Department of Animal Molecular Physiology, Institute of Experimental Biology, Wroclaw University, Wroclaw, Poland
11Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
12Dipartimento Di Scienze Biomediche E Neuromotorie, Università Di Bologna, Bologna, Italy
13Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy

Tóm tắt

Từ khóa


Tài liệu tham khảo

Cohen, 1980, Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase, Eur J Biochem, 107, 519, 10.1111/j.1432-1033.1980.tb06059.x

Woodgett, 1990, Molecular cloning and expression of glycogen synthase kinase-3/factor A, EMBO J, 9, 2431, 10.1002/j.1460-2075.1990.tb07419.x

Li, 2012, GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease, Reviews in the Neurosciences, 23, 1, 10.1515/rns.2011.061

Gattaz, 2012, Does lithium prevent Alzheimer's disease?, Drugs & Aging, 29, 335, 10.2165/11599180-000000000-00000

Agam, 2011, The possible involvement of glycogen synthase kinase-3 (GSK-3) in diabetes, cancer and central nervous system diseases, Current Pharmaceutical Design, 17, 2264, 10.2174/138161211797052484

Sollott, 2009, Role of glycogen synthase kinase-3[beta] in cardioprotection, Circulation Research, 104, 1240, 10.1161/CIRCRESAHA.109.197996

Shimura, 2011, Acquired radioresistance of cancer and the AKT/GSK3beta/cyclin D1 overexpression cycle, Journal of Radiation Research, 52, 539, 10.1269/jrr.11098

Lu, 2011, Overexpression of glycogen synthase kinase-3 in ovarian carcinoma cells with acquired paclitaxel resistance, International Journal of Gynecological Cancer, 21, 439, 10.1097/IGC.0b013e31820d7366

Tomita, 2012, GSK-3 inhibition in vitro and in vivo enhances antitumor effect of sorafenib in renal cell carcinoma (RCC), Biochemical & Biophysical Research Communications, 423, 490, 10.1016/j.bbrc.2012.05.147

Thamilselvan, 2011, Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 beta/beta-catenin pathway, International Journal of Cancer, 129, 2916, 10.1002/ijc.25949

Bone, 2011, Controlling embryonic stem cell proliferation and pluripotency: the role of PI3K- and GSK-3-dependent signalling, Biochemical Society Transactions, 39, 674, 10.1042/BST0390674

So, 2012, Selective treatment of mixed-lineage leukemia leukemic stem cells through targeting glycogen synthase kinase 3 and the canonical Wnt/[beta]-catenin pathway, Current Opinion in Hematology, 19, 280, 10.1097/MOH.0b013e3283545615

Smith, 2010, The ground state of pluripotency, Biochemical Society Transactions, 38, 1027, 10.1042/BST0381027

Zhou, 2010, GSK3 signalling in neural development, Nature Reviews Neuroscience, 11, 539, 10.1038/nrn2870

Force, 2011, Targeting GSK-3 family members in the heart: a very sharp double-edged sword, Journal of Molecular & Cellular Cardiology, 51, 607, 10.1016/j.yjmcc.2010.11.020

Zhu, 2011, beta-catenin as a potential key target for tumor suppression, International Journal of Cancer, 129, 1541, 10.1002/ijc.26102

Martinez, 2011, The potential role of glycogen synthase kinase 3 inhibitors as amyotrophic lateral sclerosis pharmacological therapy, Current Medicinal Chemistry, 18, 3028, 10.2174/092986711796391697

Gao, 2011, GSK-3beta activity and hyperdopamine-dependent behaviors, Neurosci Biobehav Rev, 35, 645, 10.1016/j.neubiorev.2010.08.001

Martin, 2011, Glycogen synthase kinase 3: a point of convergence for the host inflammatory response, Cytokine, 53, 130, 10.1016/j.cyto.2010.10.009

Christensen, 2010, Lithium-induced nephrogenic diabetes insipidus: new clinical and experimental findings, Journal of Nephrology, 23, S43

Dolnikov, 2010, Using small molecule GSK3beta inhibitors to treat inflammation, Current Medicinal Chemistry, 17, 2873, 10.2174/092986710792065090

Gomez, 2010, QSAR, docking, and CoMFA studies of GSK3 inhibitors, Current Pharmaceutical Design, 16, 2666, 10.2174/138161210792389225

Weaver, 2010, The development of new therapeutics for Alzheimer's disease, Clinical Pharmacology & Therapeutics, 88, 475, 10.1038/clpt.2010.165

Henriksen, 2010, Dysregulation of glycogen synthase kinase-3 in skeletal muscle and the etiology of insulin resistance and type 2 diabetes, Current Diabetes Reviews, 6, 285, 10.2174/157339910793360888

Javitch, 2010, Signaling pathways in schizophrenia: emerging targets and therapeutic strategies, Trends in Pharmacological Sciences, 31, 381, 10.1016/j.tips.2010.05.004

Yoon, 2010, Roles of GSK3 in metabolic shift toward abnormal anabolism in cell senescence, Annals of the New York Academy of Sciences, 1201, 65, 10.1111/j.1749-6632.2010.05617.x

Woodgett, 2000, Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation, Nature, 406, 86, 10.1038/35017574

Woodgett, 2008, Glycogen synthase kinase-3 and cancer: good cop, bad cop?, Cancer Cell, 14, 351, 10.1016/j.ccr.2008.10.013

Woodgett, 2003, GSK-3: tricks of the trade for a multi-tasking kinase, J Cell Sci, 116, 1175, 10.1242/jcs.00384

Sutherland, 2011, What are the bona fide GSK3 substrates?, International journal of Alzheimer's Disease, 23 pages

Woodgett, 2007, Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism, Cell Metab, 6, 329, 10.1016/j.cmet.2007.08.013

Woodgett, 2009, Abnormalities in brain structure and behavior in GSK-3alpha mutant mice, Mol Brain, 2, 35, 10.1186/1756-6606-2-35

Sutherland, 2010, J Evidence that glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain, Neurochem, 115, 974, 10.1111/j.1471-4159.2010.06988.x

Stegmaier, 2012, The intersection of genetic and chemical genomic screens identifies GSK-3alpha as a target in human acute myeloid leukemia, J Clin Invest, 122, 935, 10.1172/JCI46465

Mills, 2000, Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A, Proc Natl Acad Sci USA, 24, 11960

Mostov, 2007, Polarity proteins PAR6 and aPKC regulate cell death through GSK-3beta in 3D epithelial morphogenesis, J Cell Sci, 120, 2309, 10.1242/jcs.007443

Hemmings, 1995, Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B, Nature, 378, 785, 10.1038/378785a0

Woodgett, 1994, Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation, Biochem J, 303, 701, 10.1042/bj3030701

Cohen, 1993, Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling, Biochem J, 296, 15, 10.1042/bj2960015

Woodgett, 2006, Glycogen synthase kinase-3--an overview of an over-achieving protein kinase, Curr Drug Targets, 7, 1377, 10.2174/1389450110607011377

Cohen, 1994, The mechanism by which epidermal growth factor inhibits glycogen synthase kinase 3 in A431cells, Biochem J, 303, 27, 10.1042/bj3030027

Saltiel, 1998, The activation of glycogen synthase by insulin switches from kinase inhibition to phosphatase activation during adipogenesis in 3T3-L1 cells, J Biol Chem, 273, 14063, 10.1074/jbc.273.23.14063

Biondi, 2001, A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation, Mol Cell, 7, 1321, 10.1016/S1097-2765(01)00253-2

Zhao, 2009, Structural basis for the complete loss of GSK3beta catalytic activity due to R96 mutation investigated by molecular dynamics study, Proteins, 75, 671, 10.1002/prot.22279

Cohen, 2004, Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event, Biochem J, 377, 249, 10.1042/bj20031259

Woodgett, 1993, Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation, EMBO J, 12, 803, 10.1002/j.1460-2075.1993.tb05715.x

Lee, 2000, Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3beta in cellular and animal models of neuronal degeneration, Proc Natl Acad Sci USA, 97, 11074, 10.1073/pnas.190297597

Jope, 2001, Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3 beta, J Biol Chem, 276, 37436, 10.1074/jbc.M105725200

Lee, 2010, Antidiabetic effect of propolis: reduction of expression of glucose-6-phosphatase through inhibition of Y279 and Y216 autophosphorylation of GSK-3α/β in HepG2 cells, Phytother Res, 24, 1554, 10.1002/ptr.3147

Gajkowska, 2009, Alzheimer's disease genetic mutation evokes ultrastructural alterations: correlation to an intracellular Abeta deposition and the level of GSK-3beta-P(Y216) phosphorylated form, Neurotoxicology, 30, 581, 10.1016/j.neuro.2009.05.008

Ossowska, 2011, Glycogen synthase kinase 3β and its phosphorylated form (Y216) in the paraquat-induced model of parkinsonism, Neurotox Res, 19, 162, 10.1007/s12640-010-9153-7

Pei, 2011, Interplay between glycogen synthase kinase-3β and tau in the cerebellum of Hsp27 transgenic mouse, J Neurosci Res, 89, 1267, 10.1002/jnr.22660

Johnson, 2001, Glycogen synthase kinase 3beta is tyrosine phosphorylated by PYK2, Biochem Biophys Res Commun, 284, 485, 10.1006/bbrc.2001.4986

Moolenaar, 2006, GSK-3 is activated by the tyrosine kinase Pyk2 during LPA1-mediated neurite retraction, Mol Biol Cell, 17, 1834, 10.1091/mbc.e05-07-0688

Wandosell, 2011, Deconstructing GSK-3: The fine regulation of its activity, Int J Alzheimers Dis, 2011, 479249

Johnson, 1999, Insulin transiently increases tau phosphorylation: involvement of glycogen synthase kinase-3beta and Fyn tyrosine kinase, J Neurochem, 72, 576, 10.1046/j.1471-4159.1999.0720576.x

Rincon, 2008, Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation, Science, 320, 667, 10.1126/science.1156037

Iqbal, 2000, Role of protein phosphatase-2A and -1 in the regulation of GSK-3, cdk5 and cdc2 and the phosphorylation of tau in rat forebrain, FEBS Lett, 485, 87, 10.1016/S0014-5793(00)02203-1

Kimmel, 2002, Receptor-dependent and tyrosine phosphatase-mediated inhibition of GSK3 regulates cell fate choice, Dev Cell, 3, 523, 10.1016/S1534-5807(02)00269-1

Cooper, 2011, A GSK-3-mediated transcriptional network maintains repression of immediate early genes in quiescent cells, Cell Cycle, 10, 3072, 10.4161/cc.10.18.17321

Yoon, 2011, Glycogen synthase kinase (GSK)-3 promotes p70 ribosomal protein S6 kinase (p70S6K) activity and cell proliferation, Proc Natl Acad Sci USA, 108, 1204, 10.1073/pnas.1110195108

Yoon, 2012, Glycogen synthase kinase (GSK)-3 and mammalian target of rapamycin complex 1 (mTORC1) cooperate to regulate protein S6 kinase 1 (S6K1), Cell Cycle, 11, 1053, 10.4161/cc.11.6.19784

Measday, 2012, The Mck1 GSK-3 kinase inhibits the activity of Clb2-Cdk1 post-nuclear division, Cell Cycle, 11, 3421, 10.4161/cc.21731

Cleary, 2008, Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy, Nature, 455, 1205, 10.1038/nature07284

Dimmeler, 2002, Glycogen synthase kinase-3 couples AKT-dependent signaling to the regulation of p21Cip1 degradation, J Biol Chem, 277, 9684, 10.1074/jbc.M106157200

Sherr, 1998, Glycogen synthase kinase- 3beta regulates cyclin D1 proteolysis and subcellular localization, Genes Dev, 12, 3499, 10.1101/gad.12.22.3499

Roberts, 2003, Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation, Mol Cell, 12, 381, 10.1016/S1097-2765(03)00287-9

Paramio, 2002, Expression, localization, and activity of glycogen synthase kinase 3beta during mouse skin tumorigenesis, Mol Carcinog, 35, 180, 10.1002/mc.10087

Mishra, 2010, Glycogen synthase kinase 3 beta: can it be a target for oral cancer?, Molecular Cancer, 9, 144, 10.1186/1476-4598-9-144

Nakayama, 2004, Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7, EMBO J, 23, 2116, 10.1038/sj.emboj.7600217

Woodgett, 2000, Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation, Nature, 406, 86, 10.1038/35017574

Perkins, 2010, Phosphorylation of the p52 NF-kappaB subunit, Cell Cycle, 9, 4774, 10.4161/cc.9.24.14246

Ozawa, 2008, Snail regulates cell-matrix adhesion by regulation of the expression of integrins and basement membrane proteins, J Biol Chem, 283, 23514, 10.1074/jbc.M801125200

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

Nye, 2002, Glycogen synthase kinase-3beta modulates notch signaling and stability, Curr Biol, 12, 1006, 10.1016/S0960-9822(02)00888-6

Datta, 2011, Role of STRAP in regulating GSK3beta function and Notch3 stabilization, Cell Cycle, 10, 1639, 10.4161/cc.10.10.15630

Wickrema, 2002, Regulation of myeloma cell growth through Akt/Gsk3/forkhead signaling pathway, Biochem Biophys Res Commun, 297, 760, 10.1016/S0006-291X(02)02278-7

MacDougald, 1999, Glycogen synthase kinase 3 is an insulin-regulated C/EBPalpha kinase, Mol Cell Biol, 19, 8433, 10.1128/MCB.19.12.8433

Sassone-Corsi, 1993, Negative regulation of Jun/AP-1: conserved function of glycogen synthase kinase 3 and the Drosophila kinase shaggy, Oncogene, 8, 841

Kracht, 2004, Phosphorylation of serine 468 by GSK-3beta regulates basal p65 NF-kappaB activity, J Biol Chem, 279, 49571, 10.1074/jbc.C400442200

Wang, 2009, Bleomycin-induced nuclear factor kappaB activation in human bronchial epithelial cells involves the phosphorylation of glycogen synthase kinase 3beta, Toxicol Lett, 187, 194, 10.1016/j.toxlet.2009.02.023

Maggirwar, 2003, Glycogen synthase kinase 3beta-mediated apoptosis of primary cortical astrocytes involves inhibition of nuclear factor kappaB signaling, Mol Cell Biol, 23, 4649, 10.1128/MCB.23.13.4649-4662.2003

Koromilas, 2004, Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta, Genes Dev, 18, 261, 10.1101/gad.1165804

Maurer, 2011, GSK-3 turns p53 deadly, Cell Cycle, 10, 3621, 10.4161/cc.10.21.17852

Yook, 2011, A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition, J Cell Biol, 195, 417, 10.1083/jcb.201103097

Weiss, 2011, p53 and microRNA-34 are suppressors of canonical Wnt signaling, Sci Signal, 4, ra71

Villa-Moruzzi, 2005, Regulation of FAK Ser-722 phosphorylation and kinase activity by GSK3 and PP1 during cell spreading and migration, Biochem J, 391, 359, 10.1042/BJ20050282

García De Herreros, 2000, The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells, Nat Cell Biol, 2, 84, 10.1038/35000034

Mercurio, 2005, Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition, J Cell Biol, 168, 29, 10.1083/jcb.200409067

Bauer, 2009, P-cadherin induces an epithelial-like phenotype in oral squamous cell carcinoma by GSK-3beta-mediated Snail phosphorylation, Carcinogenesis, 30, 1781, 10.1093/carcin/bgp175

Du, 2013, Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer, PLoS One, 8, e56664, 10.1371/journal.pone.0056664

Jiang, 2013, Glycogen synthase kinase-3beta regulates Snail and β-catenin expression during Fas-induced epithelial-mesenchymal transition in gastrointestinal cancer, Eur J Cancer, 49, 2734, 10.1016/j.ejca.2013.03.014

Wang, 2012, Cyclin G1-mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitates liver cancer progression, Hepatology, 55, 1787, 10.1002/hep.25596

Gu, 2012, Hepatitis B virus X protein promotes hepatoma cell invasion and metastasization by stabilizing Snail protein, Cancer Sci, 103, 2072, 10.1111/cas.12017

Guan, 2014, Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3β/Snail signaling, Hepatology, 59, 531, 10.1002/hep.26677

El-Rifai, 2008, t-Darpp promotes cancer cell survival by up-regulation of Bcl2 through Akt-dependent mechanism, Cancer Res, 68, 395, 10.1158/0008-5472.CAN-07-1580

Hung, 2007, Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization, Molecular & Cellular Biology, 27, 4006, 10.1128/MCB.00620-06

Davis, 2009, Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis, Mol Cell Biol, 29, 3845, 10.1128/MCB.00279-09

Wei, 2011, Mcl-1 ubiquitination and destruction, Oncotarget, 2, 239, 10.18632/oncotarget.242

Craig, 2012, Thr 163 phosphorylation causes Mcl-1 stabilization when degradation is independent of the adjacent GSK3-targeted phosphodegron, promoting drug resistance in cancer, PLoS One, 7, e47060, 10.1371/journal.pone.0047060

Rathmell, 2007, Glycogen synthase kinase 3alpha and 3beta mediate a glucose-sensitive antiapoptotic signaling pathway to stabilize Mcl-1, Molecular & Cellular Biology, 27, 4328, 10.1128/MCB.00153-07

Lin, 2011, Increased galectin-3 facilitates leukemia cell survival from apoptotic stimuli, Biochem Biophys Res Commun, 412, 334, 10.1016/j.bbrc.2011.07.099

Hong, 2012, GSK3beta regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl, Cell Cycle, 11, 532, 10.4161/cc.11.3.19051

Lin, 2012, Anesthetic propofol causes glycogen synthase kinase-3[beta]-regulated lysosomal/mitochondrial apoptosis in macrophages, Anesthesiology, 116, 868, 10.1097/ALN.0b013e31824af68a

Ten Dijke, 2011, GSK3beta inactivation induces apoptosis of leukemia cells by repressing the function of c-Myb, Mol Biol Cell, 22, 3533, 10.1091/mbc.e11-06-0483

Boucher, 2012, Inhibition of glycogen synthase kinase-3 activity triggers an apoptotic response in pancreatic cancer cells through JNK-dependent mechanisms, Carcinogenesis, 33, 529, 10.1093/carcin/bgr309

Heidenreich, 2004, Glycogen synthase kinase-3beta phosphorylates Bax and promotes its mitochondrial localization during neuronal apoptosis, Journal of Neuroscience, 24, 9993, 10.1523/JNEUROSCI.2057-04.2004

Yu, 2005, Pharmacologic modulation of glycogen synthase kinase-3beta promotes p53-dependent apoptosis through a direct Bax-mediated mitochondrial pathway in colorectal cancer cells, Cancer Res, 65, 9012, 10.1158/0008-5472.CAN-05-1226

Pouponnot, 2007, GSK-3-mediated phosphorylation enhances Maf-transforming activity, Mol Cell, 28, 584, 10.1016/j.molcel.2007.11.009

Blok, 2010, Wnt/B-catenin and sex hormone signaling in endometrial homeostasis and cancer, Oncotarget, 1, 674, 10.18632/oncotarget.201

Wang, 2010, Jagged1 expression regulated by Notch3 and Wnt/beta-catenin signaling pathways in ovarian cancer, Oncotarget, 1, 210, 10.18632/oncotarget.127

Lorenzi, 2010, Drug discovery approaches to target Wnt signaling in cancer stem cells, Oncotarget, 1, 563, 10.18632/oncotarget.191

Morrisey, 2011, Wnt and Kras signaling-dark siblings in lung cancer, Oncotarget, 2, 569, 10.18632/oncotarget.305

Rao, 2011, Cord blood stem cells revert glioma stem cell EMT by down regulating transcriptional activation of Sox2 and Twist1, Oncotarget, 2, 1028, 10.18632/oncotarget.367

Jung, 2012, Human telomerase reverse transcriptase (hTERT) is a target gene of beta-catenin in human colorectal tumors, Cell Cycle, 11, 3331, 10.4161/cc.21790

Dalton, 2012, Reconciling the different roles of Gsk3beta in “naive” and “primed” pluripotent stem cells, Cell Cycle, 11, 2991, 10.4161/cc.21110

Chien, 2012, Regulating the response to targeted MEK inhibition in melanoma: Enhancing apoptosis in NRAS- and BRAF-mutant melanoma cells with Wnt/beta-catenin activation, Cell Cycle, 11, 3724, 10.4161/cc.21645

Yook, 2012, MiRNA-34 intrinsically links p53 tumor suppressor and Wnt signaling, Cell Cycle, 11, 1273, 10.4161/cc.19618

Sgambato, 2012, The tumor suppressor HINT1 regulates MITF and beta-catenin transcriptional activity in melanoma cells, Cell Cycle, 11, 2206, 10.4161/cc.20765

Borkan, 2011, Hexokinase regulates Bax-mediated mitochondrial membrane injury following ischemic stress, Kidney Int, 79, 1207, 10.1038/ki.2010.532

Rakus, 2012, Muscle FBPase binds to cardiomyocyte mitochondria under glycogen synthase kinase-3 inhibition or elevation of cellular Ca2+ level, FEBS Lett, 586, 13, 10.1016/j.febslet.2011.11.032

Luo, 2009, Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy, Cancer Lett, 273, 194, 10.1016/j.canlet.2008.05.045

Minamoto, 2005, Deregulated GSK3beta activity in colorectal cancer: its association with tumor cell survival and proliferation, Biochem Biophys Res Commun, 334, 1365, 10.1016/j.bbrc.2005.07.041

Billadeau, 2005, Glycogen synthase kinase-3beta participates in nuclear factor kappaB-mediated gene transcription and cell survival in pancreatic cancer cells, Cancer Res, 65, 2076, 10.1158/0008-5472.CAN-04-3642

Wang, 2012, shRNA silencing glycogen synthase kinase-3 beta inhibits tumor growth and angiogenesis in pancreatic cancer, Cancer Letters, 316, 178, 10.1016/j.canlet.2011.10.033

Seldin, 2005, Kinase-inactive glycogen synthase kinase 3beta promotes Wnt signaling and mammary tumorigenesis, Cancer Res, 65, 5792, 10.1158/0008-5472.CAN-05-1021

Luo, 2007, The role of glycogen synthase kinase 3beta in the transformation of epidermal cells, Cancer Res, 67, 7756, 10.1158/0008-5472.CAN-06-4665

Meric-Bernstam, 2005, Role of glycogen synthase kinase 3beta in rapamycin-mediated cell cycle regulation and chemosensitivity, Cancer Res, 65, 1961, 10.1158/0008-5472.CAN-04-2501

Dolcetti, 2008, GSK-3beta inhibition: at the crossroad between Akt and mTOR constitutive activation to enhance cyclin D1 protein stability in mantle cell lymphoma, Cell Cycle, 7, 2813, 10.4161/cc.7.18.6733

Xu, 2006, Adiponectin modulates the glycogen synthase kinase-3beta/betacatenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice, Cancer Res, 66, 11462, 10.1158/0008-5472.CAN-06-1969

Bartek, 1994, Cyclin D1 protein expression and function in human breast cancer, Int J Cancer, 57, 353, 10.1002/ijc.2910570311

Peters, 1994, Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining, Cancer Res, 54, 1812

Peters, 1995, Amplification of chromosome band 11q13 and a role for cyclin D1 in human breast cancer, Cancer Lett, 90, 43, 10.1016/0304-3835(94)03676-A

Hung, 2000, Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression, Proc Natl Acad Sci USA, 97, 4262, 10.1073/pnas.060025397

Costantini, 2001, Impaired mammary gland and lymphoid development caused by inducible expression of Axin in transgenic mice, J Cell Biol, 155, 1055, 10.1083/jcb.200107066

Seldin, 2001, Protein kinase CK2: signaling and tumorigenesis in the mammary gland, Mol Cell Biochem, 227, 153, 10.1023/A:1013108822847

McCubrey, 2014, Inhibition of GSK-3β activity can result in drug and hormonal resistance and alter sensitivity to targeted therapy in MCF-7 breast cancer cells, Cell Cycle

Larsson, 2000, c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover, Blood, 95, 2104, 10.1182/blood.V95.6.2104

Penn, 2002, The myc oncogene: MarvelouslY Complex, Adv Cancer Res, 84, 81, 10.1016/S0065-230X(02)84004-0

Hann, 2003, Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization, J Biol Chem, 278, 51606, 10.1074/jbc.M310722200

Zhou, 2008, DNA-dependent protein kinase catalytic subunit modulates the stability of c-Myc oncoprotein, Mol Cancer, 7, 32, 10.1186/1476-4598-7-32

Gonzalez-Baron, 2000, beta-catenin expression pattern in primary oesophageal squamous cell carcinoma. Relationship with clinicopathologic features and clinical outcome, Virchows Arch, 437, 599, 10.1007/s004280000266

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

Yura, 2005, Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma, J Cancer Res Clin Oncol, 131, 773, 10.1007/s00432-005-0027-y

Lin, 2003, Correlation between protein expression and epigenetic and mutation changes of Wnt pathway-related genes in oral cancer, Int J Oncol, 23, 1001

McCubrey, 2011, Involvement of Akt-1 and mTOR in sensitivity of breast cancer to targeted therapy, Oncotarget, 2, 538, 10.18632/oncotarget.302

McCubrey, 2011, Cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells, Oncotarget, 2, 610, 10.18632/oncotarget.315

Libra, 2012, Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance, Int J Oncol, 40, 639

McCubrey, 2011, Involvement of Akt and mTOR in chemotherapeutic- and hormonal-based drug resistance and response to radiation in breast cancer cells, Cell Cycle, 10, 3003, 10.4161/cc.10.17.17119

McCubrey, 2011, Targeting the translational apparatus to improve leukemia therapy: roles of the PI3K/PTEN/Akt/mTOR pathway, Leukemia, 25, 1064, 10.1038/leu.2011.46

Milella, 2011, Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging, Aging, 3, 192, 10.18632/aging.100296

Vogt, 2011, Phosphorylation of AKT: a mutational analysis, Oncotarget, 2, 467, 10.18632/oncotarget.293

Zawel, 2010, P3Kalpha: a driver of tumor metastasis?, Oncotarget, 1, 315, 10.18632/oncotarget.162

Zhou, 2010, PI3Kalpha inhibitors that inhibit metastasis, Oncotarget, 1, 339, 10.18632/oncotarget.166

Arteaga, 2011, Will PI3K pathway inhibitors be effective as single agents in patients with cancer?, Oncotarget, 2, 1314, 10.18632/oncotarget.409

Rajewsky, 2012, Burkitt lymphomagenesis linked to MYC plus PI3K in germinal center B cells, Oncotarget, 3, 1066, 10.18632/oncotarget.726

Baiocchi, 2012, Novel targeted therapies for mantle cell lymphoma, Oncotarget, 3, 203, 10.18632/oncotarget.426

Di Cristofano, 2011, Thyrocyte-specific inactivation of p53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors, Oncotarget, 2, 1109, 10.18632/oncotarget.380

Riggins, 2011, Abrogation of PIK3CA or PIK3R1 reduces proliferation, migration, and invasion in glioblastoma multiforme cells, Oncotarget, 2, 833, 10.18632/oncotarget.346

Backer, 2010, A beta version of life: p110beta takes center stage, Oncotarget, 1, 729, 10.18632/oncotarget.207

Hoellenriegel, 2011, Phosphoinositide 3'-kinase delta: turning off BCR signaling in chronic lymphocytic leukemia, Oncotarget, 2, 737, 10.18632/oncotarget.341

Egan, 2011, Elevated PI3K signaling drives multiple breast cancer subtypes, Oncotarget, 2, 435, 10.18632/oncotarget.285

Ittmann, 2011, INPP4B: the new kid on the PI3K block, Oncotarget, 2, 321, 10.18632/oncotarget.260

McCubrey, 2012, Dual Inhibitors of phosphatidylinositol 3-kinase and mammalian target of rapamycin: a novel therapeutic strategy for acute leukemia treatment?, Oncotarget, 3, 371, 10.18632/oncotarget.477

McCubrey, 2012, Targeting the liver Kinase B1/AMP-dependent kinase pathway as a therapeutic strategy for hematological malignancies, Expert Opinion Therapeutic Targets, 16, 729, 10.1517/14728222.2012.694869

Sabatini, 2009, DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival, Cell, 137, 873, 10.1016/j.cell.2009.03.046

Martelli, 2012, A combination of temsirolimus, an allosteric mTOR inhibitor, with clofarabine as a new therapeutic option for patients withacute myeloid leukemia, Oncotarget, 3, 1615, 10.18632/oncotarget.762

Martelli, 2012, Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels, Oncotarget, 3, 811, 10.18632/oncotarget.579

Martelli, 2014, Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention, Leukemia, 28, 15, 10.1038/leu.2013.184

Martelli, 2012, AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: therapeutic implications, Leukemia, 26, 91, 10.1038/leu.2011.269

McCubrey, 2012, Targeting the liver kinase B1/AMP-activated protein kinase pathway as a therapeutic strategy for hematological malignancies, Expert Opin Ther Targets, 16, 729, 10.1517/14728222.2012.694869

Habib, 2011, Mechanism of activation of AMPK and upregulation of OGG1 by rapamycin in cancer cells, Oncotarget, 2, 958, 10.18632/oncotarget.381

Clevers, 2009, LKB1 and AMPK family signaling: the intimate link between cell polarity and energy metabolism, Physiol Rev, 89, 777, 10.1152/physrev.00026.2008

Haramis, 2011, Insights from model organisms on the functions of the tumor suppressor protein LKB1: zebrafish chips in, Aging, 3, 363, 10.18632/aging.100319

Lawler, 2010, microRNA-451: A conditional switch controlling glioma cell proliferation and migration, Cell Cycle, 9, 2742

Thor, 2011, Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions, Cell Cycle, 10, 2959, 10.4161/cc.10.17.16359

Menendez, 2011, Metformin activates an ataxia telangiectasia mutated (ATM)/Chk2-regulated DNA damage-like response, Cell Cycle, 10, 1499, 10.4161/cc.10.9.15423

Pollak, 2011, Metformin abolishes increased tumor (18)F-2-fluoro-2-deoxy-D-glucose uptake associated with a high energy diet, Cell Cycle, 10, 2770, 10.4161/cc.10.16.16219

Menendez, 2011, Micro(mi)RNA expression profile of breast cancer epithelial cells treated with the anti-diabetic drug metformin: induction of the tumor suppressor miRNA let-7a and suppression of the TGFbeta-induced oncomiR miRNA-181a, Cell Cycle, 10, 1144, 10.4161/cc.10.7.15210

McCubrey, 2012, Ectopic NGAL expression can alter sensitivity of breast cancer cells to EGFR, Bcl-2, CaM-K inhibitors and the plant natural product berberine, Cell Cycle, 11, 4447, 10.4161/cc.22786

Goncharova, 2009, PI3K/mTORC1 activation in hamartoma syndromes: therapeutic prospects, Cell Cycle, 8, 403, 10.4161/cc.8.3.7555

Tamanoi, 2009, Specific activation of mTORC1 by Rheb G-protein in vitro involves enhanced recruitment of its substrate protein, J Biol Chem, 284, 12783, 10.1074/jbc.M809207200

Tafuri, 2012, Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response, Oncotarget, 3, 954, 10.18632/oncotarget.652

McCubrey, Steelman, Chappell, Abrams, Montalto, Cervello, Nicoletti, Fagone, Malaponte, Mazzarino, Candido, Libra, Bäsecke, Mijatovic, Maksimovic-Ivanic, Cocco, et al. Oncotarget. 2012; 3:1068–1111.

Montalto, 2012, Targeted therapy for hepatocellular carcinoma: novel agents on the horizon, Oncotarget, 3, 236, 10.18632/oncotarget.466

Pandolfi, 2008, Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer, J Clin Invest, 118, 3065

Bouscary, 2009, Targeting translation in acute myeloid leukemia: a new paradigm for therapy?, Cell Cycle, 8, 3893, 10.4161/cc.8.23.10091

Martin, 2011, Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-β-signaling pathways regulates the innate inflammatory response, J Immunol, 186, 5217, 10.4049/jimmunol.1002513

Guan, 2006, TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth, Cell, 126, 955, 10.1016/j.cell.2006.06.055

Sun, 2014, Maintaining glycogen synthase kinase-3 activity is critical for mTOR kinase inhibitors to inhibit cancer cell growth, Cancer Res

Klein, 2009, Pivotal role for glycogen synthase kinase-3 in hematopoietic stem cell homeostasis in mice, J Clin Invest, 119, 3519

Morrison, 2006, Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells, Nature, 441, 475, 10.1038/nature04703

Zheng, 2008, TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species, J Exp Med, 205, 2397, 10.1084/jem.20081297

Morrison, 2010, mTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion, Cell Stem Cell, 7, 593, 10.1016/j.stem.2010.09.015

Scadden, 2006, The hematopoietic stem cell in its place, Nat Immunol, 7, 333, 10.1038/ni1331

Depinho, 2010, Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells, Nature, 468, 701, 10.1038/nature09595

Bardeesy, 2010, The Lkb1 metabolic sensor maintains haematopoietic stem cell survival, Nature, 468, 659, 10.1038/nature09572

DePinho, 2009, mTORC1 signaling governs hematopoietic stem cell quiescence, Cell Cycle, 8, 1003, 10.4161/cc.8.7.8045

Zheng, 2009, mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells, Sci Signal, 2, ra75

Klein, 2012, Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways, Nat Med, 18, 1778, 10.1038/nm.2984

Pandolfi, 2012, A PML-PPAR-delta pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance, Nat Med, 18, 1350, 10.1038/nm.2882

Vanden Heuvel, 2007, Modulation of PPAR activity via phosphorylation, Biochim Biophys Acta, 1771, 952, 10.1016/j.bbalip.2007.04.018

Arch, 2007, Thermogenic and metabolic antiobesity drugs: rationale and opportunities, Diabetes Obes Metab, 9, 259, 10.1111/j.1463-1326.2006.00608.x

Evans, 2008, AMPK and PPARdelta agonists are exercise mimetics, Cell, 134, 405, 10.1016/j.cell.2008.06.051

Pandolfi, 2008, PML targeting eradicates quiescent leukaemia-initiating cells, Nature, 453, 1072, 10.1038/nature07016

Pandolfi, 2006, PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR, Nature, 442, 779, 10.1038/nature05029

Pandolfi, 2011, Pml represses tumour progression through inhibition of mTOR, EMBO Mol Med, 3, 249, 10.1002/emmm.201100130

Brivanlou, 2004, Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor, Nat Med, 10, 55, 10.1038/nm979

Woodgett, 2007, Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines, Dev Cell, 12, 957, 10.1016/j.devcel.2007.04.001

Restifo, 2009, Pharmacologic induction of CD8+ T cell memory: better living through chemistry, Sci Transl Med, 1, 11ps12

Roederer, 2011, A human memory T cell subset with stem cell-like properties, Nat Med, 17, 1290, 10.1038/nm.2446

Restifo, 2012, Paths to stemness: building the ultimate antitumour T cell, Nat Rev Cancer, 12, 671, 10.1038/nrc3322

Nusse, 2012, Wnt/β-catenin signaling and disease, Cell, 149, 1192, 10.1016/j.cell.2012.05.012

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

Wynshaw-Boris, 2012, Wnt signaling in mammalian development: lessons from mouse genetics, Cold Spring Harb Perspect Biol, 4

Clevers, 2002, Wnt signaling controls the phosphorylation status of beta-catenin, J Biol Chem, 277, 17901, 10.1074/jbc.M111635200

Vidal-Puig, 2002, Characterisation of the phosphorylation of beta-catenin at the GSK-3 priming site Ser45, Biochem Biophys Res Commun, 294, 324, 10.1016/S0006-291X(02)00485-0

Reith, 2002, Expression and characterization of GSK-3 mutants and their effect on beta-catenin phosphorylation in intact cells, J Biol Chem, 277, 23330, 10.1074/jbc.M201364200

He, 2002, Control of beta-. catenin phosphorylation/degradation by a dual-kinase mechanism, Cell, 108, 837, 10.1016/S0092-8674(02)00685-2

Sakanaka, 2002, Phosphorylation and regulation of beta-catenin by casein kinase I epsilon, J Biochem, 132, 697, 10.1093/oxfordjournals.jbchem.a003276

Ishimoto, 2002, Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila, EMBO J, 21, 1733, 10.1093/emboj/21.7.1733

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

Costantini, 1999, A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression, Biochem Biophys Res Commun, 266, 28, 10.1006/bbrc.1999.1760

Kikuchi, 1999, Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability, J Biol Chem, 274, 10681, 10.1074/jbc.274.16.10681

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

Birchmeier, 2002, The ankyrin repeat protein Diversin recruits Casein kinase I epsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling, Genes Dev, 16, 2073, 10.1101/gad.230402

Reith, 2001, The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation, Structure, 9, 1143, 10.1016/S0969-2126(01)00679-7

Kimelman, 2002, Glycogen synthase kinase-3 beta mutagenesis identifies a common binding domain for GBP and Axin, J Biol Chem, 277, 16147, 10.1074/jbc.M112363200

Dale, 2002, The regulation of glycogen synthase kinase-3 nuclear export by Frat/GBP, J Biol Chem, 277, 43844, 10.1074/jbc.M207265200

McCormick, 2000, Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling, J Biol Chem, 275, 32475, 10.1074/jbc.M005342200

Wu, 1999, Suppression of glycogen synthase kinase activity is not sufficient for leukemia enhancer factor-1 activation, J Biol Chem, 274, 30419, 10.1074/jbc.274.43.30419

He, 2005, A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation, Nature, 438, 873, 10.1038/nature04185

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

He, 2009, Wnt/beta-catenin signaling: components, mechanisms, and diseases, Dev Cell, 17, 9, 10.1016/j.devcel.2009.06.016

Niehrs, 2005, Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction, Nature, 438, 867, 10.1038/nature04170

Pan, 2010, GSK3: a multifaceted kinase in Wnt signaling, Trends Biochem Sci, 35, 161, 10.1016/j.tibs.2009.10.002

Moon, 2007, Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling, Science, 316, 1043, 10.1126/science/1141515

Klein, 2012, Adenomatous polyposis coli (APC) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (GSK-3) activity, J Biol Chem, 287, 3823, 10.1074/jbc.M111.323337

Capeau, 2002, Dysregulation of glycogen synthase kinase-3beta signaling in hepatocellular carcinoma cells, Hepatology, 36, 1528, 10.1002/hep.1840360630

Shan, 2013, The correlation between TSC2 and GSK3β levels, and outcomes of patients with hepatocellular carcinoma treated by hepatectomy, Hepatol Res

Shan, 2013, The correlation between TSC2 and GSK3β levels, and outcomes of patients with hepatocellular carcinoma treated by hepatectomy, Hepatol Res

Capeau, 2002, Dysregulation of glycogen synthase kinase-3beta signaling in hepatocellular carcinoma cells, Hepatology, 36, 1528, 10.1002/hep.1840360630

Hung, 2005, Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin, Mol Cell, 19, 159, 10.1016/j.molcel.2005.06.009

Schaller, 2006, Glycogen synthase kinase 3-beta and extracellular signal-regulated kinase-dependent phosphorylation of paxillin regulates cytoskeletal rearrangement, Mol Cell Biol, 26, 2857, 10.1128/MCB.26.7.2857-2868.2006

Tang, 2011, Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells, PLoS One, 6, e27496, 10.1371/journal.pone.0027496

Ko, 2013, SIRT2 overexpression in hepatocellular carcinoma mediates epithelial to mesenchymal transition by protein kinase B/glycogen synthase kinase-3β/β-catenin signaling, Hepatology, 57, 2287, 10.1002/hep.26278

Verdin, 2013, The sirtuins, oxidative stress and aging: an emerging link, Aging, 5, 144, 10.18632/aging.100544

Minamoto, 2007, Inhibition of GSK-3beta activity attenuates proliferation of human colon cancer cells in rodents, Cancer Sci, 98, 1388, 10.1111/j.1349-7006.2007.00545.x

Chen, 2007, Inactivation of glycogen synthase kinase-3β, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells, Mol Cancer Ther, 6, 1151, 10.1158/1535-7163.MCT-06-0665

Herlyn, 2007, An organometallic protein kinase inhibitor pharmacologically activates p53 and induces apoptosis in human melanoma cells, Cancer Res, 67, 209, 10.1158/0008-5472.CAN-06-1538

Minamoto, 2009, Potential therapeutic effect of glycogen synthase kinase 3beta inhibition against human glioblastoma, Clin Cancer Res, 15, 887, 10.1158/1078-0432.CCR-08-0760

Hamada, 2013, Glycogen synthase kinase 3β inhibition sensitizes human glioblastoma cells to temozolomide by affecting O6-methylguanine DNA methyltransferase promoter methylation via c-Myc signaling, Carcinogenesis, 34, 2206, 10.1093/carcin/bgt182

Minamoto, 2013, Aberrant glycogen synthase kinase 3β is involved in pancreatic cancer cell invasion and resistance to therapy, PLoS One, 8, e55289, 10.1371/journal.pone.0055289

Minamoto, 2009, Deregulated GSK3beta sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase, Clin Cancer Res, 15, 6810, 10.1158/1078-0432.CCR-09-0973

Desbois-Mouthon, 2009, Glycogen synthase kinase-3 inhibitors augment TRAIL-induced apoptotic death in human hepatoma cells, Biochem Pharmacol, 77, 54, 10.1016/j.bcp.2008.09.026

Minamoto, 2009, Deregulated GSK3beta sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase, Clin Cancer Res, 15, 6810, 10.1158/1078-0432.CCR-09-0973

Desbois-Mouthon, 2009, Glycogen synthase kinase-3 inhibitors augment TRAIL-induced apoptotic death in human hepatoma cells, Biochem Pharmacol, 77, 54, 10.1016/j.bcp.2008.09.026

De Robertis, 2007, Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal, Cell, 131, 980, 10.1016/j.cell.2007.09.027

Curran, 2011, The Hedgehog's tale: developing strategies for targeting cancer, Nat Rev Cancer, 11, 493, 10.1038/nrc3079

de Sauvage, 2011, Hedgehog fights back: mechanisms of acquired resistance against smoothened antagonists, Cancer Res, 71, 5057, 10.1158/0008-5472.CAN-11-0923

Miki, 2007, GSK3beta positively regulates Hedgehog signaling through Sufu in mammalian cells, Biochem Biophys Res Commun, 353, 501, 10.1016/j.bbrc.2006.12.058

Zaphiropoulos, 1999, Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1, Nat Cell Biol, 1, 312, 10.1038/13031

Miki, 2009, Sufu recruits GSK3beta for efficient processing of Gli3, Biochem Biophys Res Commun, 387, 569, 10.1016/j.bbrc.2009.07.087

Bray, 2006, Notch signalling: a simple pathway becomes complex, Nat Rev Mol Cell Biol, 7, 678, 10.1038/nrm2009

Kopan, 1998, Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain, Nature, 393, 382, 10.1038/30756

Kopan, 1999, A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain, Nature, 398, 518, 10.1038/19083

Adachi, 1998, Nuclear access and action of notch in vivo, Cell, 93, 649, 10.1016/S0092-8674(00)81193-9

Kageyama, 1999, Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation, EMBO J, 18, 2196, 10.1093/emboj/18.8.2196

Pourquié, 2000, Notch signalling is required for cyclic expression of the hairy-like gene HES1 in the presomitic mesoderm, Development, 127, 1421, 10.1242/dev.127.7.1421

Shin, 2008, Down-regulation of Notch-dependent transcription by Akt in vitro, FEBS Lett, 582, 1693, 10.1016/j.febslet.2008.04.024

Shin, 2012, Glycogen synthase kinase 3-beta phosphorylates novel S/T-P-S/T domains in Notch1 intracellular domain and induces its nuclear localization, Biochem Biophys Res Commun, 423, 282, 10.1016/j.bbrc.2012.05.111

Kim, 2009, Regulation of Notch1/NICD and Hes1 expressions by GSK-3alpha/beta, Mol Cells, 27, 15, 10.1007/s10059-009-0001-7

Kim, 2009, Beta-catenin modulates the level and transcriptional activity of Notch1/NICD through its direct interaction, Biochim Biophys Acta, 1793, 290, 10.1016/j.bbamcr.2008.10.002

Bigas, 2003, Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways, J Biol Chem, 278, 32227, 10.1074/jbc.M304001200

Woodgett, 1996, Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells, Curr Biol, 6, 1664, 10.1016/S0960-9822(02)70790-2

Howland, 2007, Lithium: underappreciated and underused?, J Psychosoc Nurs Ment Health Serv, 45, 13, 10.3928/02793695-20070601-05

Calamandrei, 1981, Haematological effects of lithium carbonate: a study in 56 psychiatric patients, Haematologica, 66, 627

Joyce, 1983, The hematopoietic effects of lithium, Semin Hematol, 20, 129

Joyce, 1984, Sequential effects of lithium on haematopoiesis, Br J Haematol, 56, 307, 10.1111/j.1365-2141.1984.tb03958.x

Meytes, 1998, Increased number of peripheral blood CD34+ cells in lithium-treated patients, Br J Haematol, 100, 219, 10.1046/j.1365-2141.1998.00537.x

Melton, 1996, A molecular mechanism for the effect of lithium on development, Proc Natl Acad Sci USA, 93, 8455, 10.1073/pnas.93.16.8455

Klein, 1997, Activation of the Wnt signaling pathway: a molecular mechanism for lithium action, Dev Biol, 185, 82, 10.1006/dbio.1997.8552

Klein, 2001, Molecular targets of lithium action, Annu Rev Pharmacol Toxicol, 41, 789, 10.1146/annurev.pharmtox.41.1.789

Billadeau, 2008, Inhibition of glycogen synthase kinase-3, Methods Mol Biol, 468, 67, 10.1007/978-1-59745-249-6_5

Billadeau, 2007, Inhibition of glycogen synthase kinase-3 activity leads to epigenetic silencing of nuclear factor kappaB target genes and induction of apoptosis in chronic lymphocytic leukemia B cells, Blood, 110, 735, 10.1182/blood-2006-12-060947

Feng, 2006, Glycogen synthase kinase-3beta positively regulates the proliferation of human ovarian cancer cells, Cell Res, 16, 671, 10.1038/sj.cr.7310078

Minamoto, 2007, Inhibition of GSK-3 beta activity attenuates proliferation of human colon cancer cells in rodents, Cancer Sci, 98, 1388, 10.1111/j.1349-7006.2007.00545.x

Minamoto, 2009, Potential therapeutic effect of glycogen synthase kinase 3beta inhibition against human glioblastoma, Clin Cancer Res, 15, 887, 10.1158/1078-0432.CCR-08-0760

Kjeldsen-Kragh, 2012, Glycogen synthase kinase-3 (GSK-3) inhibition induces apoptosis in leukemic cells through mitochondria-dependent pathway, Leuk Res, 36, 499, 10.1016/j.leukres.2011.11.013

Cheng, 2011, Involvement of glycogen synthase kinase-3β in arsenic trioxide-induced p21 expression, Toxicol Sci, 121, 101, 10.1093/toxsci/kfr023

Coombes, 2006, Role of glycogen synthase kinase 3 beta (GSK3beta) in mediating the cytotoxic effects of the histone deacetylase inhibitor trichostatin A (TSA) in MCF-7 breast cancer cells, Mol Cancer, 5, 40, 10.1186/1476-4598-5-40

Reiss, 2007, Inhibition of IGF-I receptor in anchorage-independence attenuates GSK-3beta constitutive phosphorylation and compromises growth and survival of medulloblastoma cell lines, Oncogene, 26, 2308, 10.1038/sj.onc.1210018

Cheng, 2005, Defining the role of Wnt/beta-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells, Stem Cells, 23, 1489, 10.1634/stemcells.2005-0034

Stanton, 2007, Generation of multipotential mesendodermal progenitors from mouse embryonic stem cells via sustained Wnt pathway activation, J Biol Chem, 282, 31703, 10.1074/jbc.M704287200

Woodgett, 2009, Exploring Pluripotency with Chemical Genetics, Cell Stem Cell, 4, 98, 10.1016/j.stem.2009.01.005

Emerson, 2006, Phosphoinositide 3-kinase and Akt are essential for Sonic hedgehog signaling, Proc Nat Acad Sci USA, 103, 4505, 10.1073/pnas.0504337103

Welham, 2009, Involvement of GSK-3 in regulation of murine embryonic stem cell self-renewal revealed by a series of bisindolylmaleimides, Chem Biol, 16, 15, 10.1016/j.chembiol.2008.11.003

Minamoto, 2009, An emerging strategy for cancer treatment targeting aberrant glycogen synthase kinase 3 beta, Anticancer Agents Med Chem, 9, 1114, 10.2174/187152009789734982

Mire, 2008, GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines, Journal of Biological Chemistry, 283, 726, 10.1074/jbc.M705343200

Manji, 2009, A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients, J Clin Psychiatry, 70, 699, 10.4088/JCP.07m03745

Hong, 2011, Troglitazone, a PPAR agonist, inhibits human prostate cancer cell growth through inactivation of NFκB via suppression of GSK-3β expression, Cancer Biol Ther, 12, 288, 10.4161/cbt.12.4.15961

Bhat, 2013, AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans, J Neurochem, 125, 446, 10.1111/jnc.12203

Jonsson, 2012, GSK-3 inhibition by an orally active small molecule increases bone mass in rats, Bone, 50, 619, 10.1016/j.bone.2011.11.007

Greengard, 2003, GSK-3-selective inhibitors derived from Tyrian purple indirubins, Chem Biol, 10, 1255, 10.1016/j.chembiol.2003.11.010

MacDougald, 2005, Regulation of osteoblastogenesis and bone mass by Wnt10b, Proc Natl Acad Sci U S A, 102, 3324, 10.1073/pnas.0408742102

Harrison, 2003, Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo, Diabetes, 52, 588, 10.2337/diabetes.52.3.588

Cassidy, 2013, Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 in rats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure, Drug Metab Dispos, 41, 714, 10.1124/dmd.112.048488

Lang, 2012, GSK-3 promotes cell survival, growth, and PAX3 levels in human melanoma cells, Mol Cancer Res, 10, 1065, 10.1158/1541-7786.MCR-11-0387

Semenzato, 2010, Glycogen Synthase Kinase-3 regulates multiple myeloma cell growth and bortezomib-induced cell death, BMC Cancer, 10, 526, 10.1186/1471-2407-10-526

Thotala, 2011, GSK-3β inhibition promotes cell death, apoptosis, and in vivo tumor growth delay in neuroblastoma Neuro-2A cell line, J Neurooncol, 104, 145, 10.1007/s11060-010-0491-3

Desbois-Mouthon, 2009, Glycogen synthase kinase-3 inhibitors augment TRAIL-induced apoptotic death in human hepatoma cells, Biochem Pharmacol, 77, 54, 10.1016/j.bcp.2008.09.026

Perez-Castillo, 2010, Inhibition of glioblastoma growth by the thiadiazolidinone compound TDZD-8, PLoS One, 5, e13879, 10.1371/journal.pone.0013879

Chen, 2010, Glycogen synthase kinase 3 regulates PAX3-FKHR-mediated cell proliferation in human alveolar rhabdomyosarcoma cells, Biochem Biophys Res Commun, 391, 1049, 10.1016/j.bbrc.2009.12.017

León, 2013, Treatment of Alzheimer's disease with the GSK-3 inhibitor tideglusib: a pilot study, J Alzheimers Dis, 33, 205