Could drugs inhibiting the mevalonate pathway also target cancer stem cells?

Drug Resistance Updates - Tập 25 - Trang 13-25 - 2016
Wirginia Likus1, Krzysztof Siemianowicz2, Konrad Bieńk3, Malgorzata M. Pakula4, Himani Pathak5, Chhanda Dutta6, Qiong Wang7, Shahla Shojaei8, Yehuda G. Assaraf9, Saeid Ghavami10,11, Artur Cieślar‐Pobuda12, Marek Łos13,14
1Department of Human Anatomy, School of Medicine in Katowice, Medical University of Silesia, 18 Medyków Street, 40-752 Katowice, Poland
2Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, 18 Medyków Street, 40-752 Katowice, Poland
3Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark
4Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark
5Indian Institute of Science Education and Research (IISER TVM), Thiruvananthapuram, Kerala, India
6Department of Clinical & Experimental Medicine (IKE), Linköping University, Linköping, Sweden
7Department of Physics, Chemistry and Biology (IFM), Division of Biotechnology, Linköping University, Linköping, Sweden
8Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
9The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel
10Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
11Health Research Policy Center, Shiraz University of Medical Science, Shiraz, Iran
12Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland
13ENT Department, School of Medicine in Katowice, Medical University of Silesia, 20-24 Francuska Street, 40-027 Katowice, Poland
14LinkoCare Life Sciences AB, 583 30 Linköping, Sweden

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Adini, 2003, RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development, Genes Dev., 17, 2721, 10.1101/gad.1134603

Aggeler, 2002, A functionally active human F1F0 ATPase can be purified by immunocapture from heart tissue and fibroblast cell lines. Subunit structure and activity studies, J. Biol. Chem., 277, 33906, 10.1074/jbc.M204538200

Appels, 2005, Development of farnesyl transferase inhibitors: a review, Oncologist, 10, 565, 10.1634/theoncologist.10-8-565

Appels, 2005, Quantitative analysis of the farnesyl transferase inhibitor lonafarnib (Sarasar(TM), SCH66336) in human plasma using high-performance liquid chromatography coupled with tandem mass spectrometry, Rapid Commun. Mass Spectrom., 19, 2187, 10.1002/rcm.2046

Asad, 2014, FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway, Cell Death Dis., 5, e1346, 10.1038/cddis.2014.302

Assaraf, 2007, Molecular basis of antifolate resistance, Cancer Metastasis Rev., 26, 153, 10.1007/s10555-007-9049-z

Basso, 2006, Farnesyl transferase inhibitors, J. Lipid Res., 47, 15, 10.1194/jlr.R500012-JLR200

Berndt, 2011, Targeting protein prenylation for cancer therapy, Nat. Rev. Cancer, 11, 775, 10.1038/nrc3151

Bhat, 2011, The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma, Genes Dev., 25, 2594, 10.1101/gad.176800.111

Bhattacharya, 2015, KRAS mutant lung cancer: progress thus far on an elusive therapeutic target, Clin. Transl. Med., 4, 35, 10.1186/s40169-015-0075-0

Bonetti, 2003, Statin effects beyond lipid lowering—are they clinically relevant?, Eur. Heart J., 24, 225, 10.1016/S0195-668X(02)00419-0

Bos, 1989, Ras oncogenes in human cancer: a review, Cancer Res., 49, 4682

Boureux, 2007, Evolution of the Rho family of Ras-like GTPases in eukaryotes, Mol. Biol. Evol., 24, 203, 10.1093/molbev/msl145

Brown, 1974, Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and inhibition of growth of human fibroblasts by 7-ketocholesterol, J. Biol. Chem., 249, 7306, 10.1016/S0021-9258(19)42106-6

Brown, 1980, Multivalent feedback-regulation of Hmg Coa Reductase, a control mechanism coordinating isoprenoid synthesis and cell-growth, J. Lipid Res., 21, 505, 10.1016/S0022-2275(20)42221-7

Brunner, 2003, Farnesyltransferase inhibitors: an overview of the results of preclinical and clinical investigations, Cancer Res., 63, 5656

Buhaescu, 2007, Mevalonate pathway: a review of clinical and therapeutical implications, Clin. Biochem., 40, 575, 10.1016/j.clinbiochem.2007.03.016

Burg, 2011, Regulation of HMG-CoA reductase in mammals and yeast, Prog. Lipid Res., 50, 403, 10.1016/j.plipres.2011.07.002

Casey, 1996, Protein prenyltransferases, J. Biol. Chem., 271, 5289, 10.1074/jbc.271.10.5289

Chaabane, 2014, Human-gyrovirus-Apoptin triggers mitochondrial death pathway--Nur77 is required for apoptosis triggering, Neoplasia (New York, NY), 16, 679, 10.1016/j.neo.2014.08.001

Choy, 1999, Endomembrane trafficking of Ras: the CAAX motif targets proteins to the ER and Golgi, Cell, 98, 69, 10.1016/S0092-8674(00)80607-8

Clark, 2000, Genomic analysis of metastasis reveals an essential role for RhoC, Nature, 406, 532, 10.1038/35020106

Cox, 1992, Specific isoprenoid modification is required for function of normal, but not oncogenic, Ras protein, Mol. Cell. Biol., 12, 2606, 10.1128/MCB.12.6.2606

Coxon, 2004, Zoledronic acid induces apoptosis and inhibits adhesion to mineralized matrix in prostate cancer cells via inhibition of protein prenylation, BJU Int., 94, 164, 10.1111/j.1464-4096.2004.04831.x

Crul, 2001, Ras biochemistry and farnesyl transferase inhibitors: a literature survey, Anti-Cancer Drug, 12, 163, 10.1097/00001813-200103000-00001

DeBose-Boyd, 2008, Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase, Cell Res., 18, 609, 10.1038/cr.2008.61

Denoyelle, 2001, Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness and metastatic properties of highly invasive breast cancer cell lines: an in vitro study, Carcinogenesis, 22, 1139, 10.1093/carcin/22.8.1139

Denoyelle, 2003, New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and -independent effects, Br. J. Cancer, 88, 1631, 10.1038/sj.bjc.6600925

Di Chiara, 2009, Does surveillance impact on cardiovascular prevention?, Eur. Heart J., 30, 1027, 10.1093/eurheartj/ehp025

Du, 1999, Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB, Mol. Cell. Biol., 19, 1831, 10.1128/MCB.19.3.1831

Ellenbroek, 2007, Rho GTPases: functions and association with cancer, Clin. Exp. Metastasis, 24, 657, 10.1007/s10585-007-9119-1

Farahani, 2014, Cell adhesion molecules and their relation to (cancer) cell stemness, Carcinogenesis, 35, 747, 10.1093/carcin/bgu045

Fernandez, 2004, Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation, Exp. Cell Res., 300, 109, 10.1016/j.yexcr.2004.06.029

Fernandez, 2014, The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells, Proc. Natl. Acad. Sci. U.S.A., 111, 1409, 10.1073/pnas.1323697111

Fleisch, 1991, Bisphosphonates. Pharmacology and use in the treatment of tumour-induced hypercalcaemic and metastatic bone disease, Drugs, 42, 919, 10.2165/00003495-199142060-00003

Fleisch, 1998, Bisphosphonates: mechanisms of action, Endocrine Rev., 19, 80, 10.1210/edrv.19.1.0325

Frick, 2003, Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells, Atherosclerosis, 170, 229, 10.1016/S0021-9150(03)00299-5

Fritz, 2009, Targeting the mevalonate pathway for improved anticancer therapy, Curr. Cancer Drug Targets, 9, 626, 10.2174/156800909789057033

Gaist, 2014, Statin use and survival following glioblastoma multiforme, Cancer Epidemiol., 38, 722, 10.1016/j.canep.2014.09.010

Gauthaman, 2009, Statins, stem cells, and cancer, J. Cell. Biochem., 106, 975, 10.1002/jcb.22092

Ghavami, 2012, Apoptosis, autophagy and ER stress in mevalonate cascade inhibition-induced cell death of human atrial fibroblasts, Cell Death Dis., 3, e330, 10.1038/cddis.2012.61

Ghavami, 2012, Geranylgeranyl transferase 1 modulates autophagy and apoptosis in human airway smooth muscle, Am. J. Physiol. Lung Cell. Mol. Physiol., 302, L420, 10.1152/ajplung.00312.2011

Ghavami, 2014, Airway mesenchymal cell death by mevalonate cascade inhibition: integration of autophagy, unfolded protein response and apoptosis focusing on Bcl2 family proteins, Biochim. Biophys. Acta, 1843, 1259, 10.1016/j.bbamcr.2014.03.006

Goldstein, 1990, Regulation of the mevalonate pathway, Nature, 343, 425, 10.1038/343425a0

Gonen, 2012, Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance, Drug Resist. Updates, 15, 183, 10.1016/j.drup.2012.07.002

Graaf, 2004, Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer, Cancer Treat. Rev., 30, 609, 10.1016/j.ctrv.2004.06.010

Graaf, 2004, The risk of cancer in users of statins, J. Clin. Oncol., 22, 2388, 10.1200/JCO.2004.02.027

Gunde-Cimerman, 1995, Pleurotus fruiting bodies contain the inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase-lovastatin, Exp. Mycol., 19, 1, 10.1006/emyc.1995.1001

Haeffner, 1984, Cholesterol-induced growth stimulation, cell aggregation, and membrane properties of ascites tumor cells in culture, Cancer Res., 44, 2668

Hall, 1998, Rho GTPases and the actin cytoskeleton, Science, 279, 509, 10.1126/science.279.5350.509

Hamilton, 2007, The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1,2 that sustain high basal motility in breast cancer cells, J. Biol. Chem., 282, 16667, 10.1074/jbc.M702078200

Hancock, 1989, All Ras proteins are polyisoprenylated but only some are palmitoylated, Cell, 57, 1167, 10.1016/0092-8674(89)90054-8

Harvey, 2013, The Hippo pathway and human cancer, Nat. Rev. Cancer, 13, 246, 10.1038/nrc3458

Hinson, 1997, Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways, J. Lipid Res., 38, 2216, 10.1016/S0022-2275(20)34935-X

Holdgate, 2003, Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin, Biochem. Soc. Trans., 31, 528, 10.1042/bst0310528

Huang, 2006, RhoB in cancer suppression, Histol. Histopathol., 21, 213

Iishi, 2000, Ras p21 Isoprenylation inhibition induces flat colon tumors in Wistar rats, Dis. Colon Rectum, 43, 70, 10.1007/BF02237247

Istvan, 2002, Structural mechanism for statin inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, Am. Heart J., 144, S27, 10.1067/mhj.2002.130300

Istvan, 2003, Statin inhibition of HMG-CoA reductase: a 3-dimensional view, Atherosclerosis Suppl., 4, 3, 10.1016/S1567-5688(03)00003-5

Jackson, 1990, Farnesol modification of Kirsten-Ras Exon 4b-protein is essential for transformation, Proc. Natl. Acad. Sci. U.S.A., 87, 3042, 10.1073/pnas.87.8.3042

Jain, 2015, Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21(Waf1/Cip1) and p27(kip1), Cell Cycle (Georgetown, Tex), 14, 2109, 10.1080/15384101.2015.1041692

Jangamreddy, 2013, Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells, Biochim. Biophys. Acta, 1833, 2057, 10.1016/j.bbamcr.2013.04.011

Jaswal, 2003, Role of C-reactive protein in deciding duration of antibiotic therapy in neonatal septicemia, Indian Pediatr., 40, 880

Jick, 2000, Statins and the risk of dementia, Lancet, 356, 1627, 10.1016/S0140-6736(00)03155-X

Kalluri, 2009, The basics of epithelial-mesenchymal transition, J. Clin. Investig., 119, 1420, 10.1172/JCI39104

Kamai, 2004, Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer, Clin. Cancer Res., 10, 4799, 10.1158/1078-0432.CCR-0436-03

Kato, 1992, Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity, Proc. Natl. Acad. Sci. U.S.A., 89, 6403, 10.1073/pnas.89.14.6403

Katoh, 2005, WNT/PCP signaling pathway and human cancer (review), Oncol. Rep., 14, 1583

Keep, 1997, A modulator of rho family G proteins, rhoGDI, binds these G proteins via an immunoglobulin-like domain and a flexible N-terminal arm, Structure, 5, 623, 10.1016/S0969-2126(97)00218-9

Keyomarsi, 1991, Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin, Cancer Res., 51, 3602

Koo, 2014, Oct4 is a critical regulator of stemness in head and neck squamous carcinoma cells, Oncogene, 34, 2317, 10.1038/onc.2014.174

Kotwal, 2013, Molecular markers unravel intraspecific and interspecific genetic variability in Plantago ovata and some of its wild allies, J. Genet., 92, 293, 10.1007/s12041-013-0240-4

Koyuturk, 2004, Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-jun N-terminal kinase, Neurosci. Lett., 370, 212, 10.1016/j.neulet.2004.08.020

Lebowitz, 1997, Prenylation of RhoB is required for its cell transforming function but not its ability to activate serum response element-dependent transcription, J. Biol. Chem., 272, 16093, 10.1074/jbc.272.26.16093

Lee, 2007, Simvastatin suppresses self-renewal of mouse embryonic stem cells by inhibiting RhoA geranylgeranylation, Stem Cells (Dayton, Ohio), 25, 1654, 10.1634/stemcells.2006-0753

Lee, 2014, Wnt/beta-catenin signalling maintains self-renewal and tumourigenicity of head and neck squamous cell carcinoma stem-like cells by activating Oct4, J. Pathol., 234, 99, 10.1002/path.4383

Lennernas, 1997, Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences, Clin. Pharmacokinet., 32, 403, 10.2165/00003088-199732050-00005

Li, 2004, Transformation potential of Ras isoforms correlates with activation of phosphatidylinositol 3-kinase but not ERK, J. Biol. Chem., 279, 37398, 10.1074/jbc.M405730200

Li, 2012, The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/beta-catenin signaling and silenced in common carcinomas, Oncogene, 31, 3901, 10.1038/onc.2011.541

Liu, 2001, RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage, Proc. Natl. Acad. Sci. U.S.A., 98, 6192, 10.1073/pnas.111137198

Liu, 2006, Herbal medicines for treatment of irritable bowel syndrome, Cochrane Database Syst. Rev., 25, CD004116

Livney, 2013, Rationally designed nanovehicles to overcome cancer chemoresistance, Adv. Drug Delivery Rev., 65, 1716, 10.1016/j.addr.2013.08.006

Lobell, 2001, Evaluation of farnesyl: protein transferase and geranylgeranyl: protein transferase inhibitor combinations in preclinical models, Cancer Res., 61, 8758

Ma, 1986, Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits, Proc. Natl. Acad. Sci. U.S.A., 83, 8370, 10.1073/pnas.83.21.8370

Maddika, 2009, Unscheduled Akt-triggered activation of cyclin-dependent kinase 2 as a key effector mechanism of apoptin's anticancer toxicity, Mol. Cell. Biol., 29, 1235, 10.1128/MCB.00668-08

Magnusson, 2015, Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte, Cytometry A, 87, 262, 10.1002/cyto.a.22627

Maltese, 1985, Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, J. Clin. Investig., 76, 1748, 10.1172/JCI112165

Maurer-Stroh, 2005, Refinement and prediction of protein prenylation motifs, Genome Biol., 6, R55, 10.1186/gb-2005-6-6-r55

Maurer-Stroh, 2003, Protein prenyltransferases, Genome Biol., 4, 212, 10.1186/gb-2003-4-4-212

Melchior, 2008, The WNT receptor FZD7 contributes to self-renewal signaling of human embryonic stem cells, Biol. Chem., 389, 897, 10.1515/BC.2008.108

Mijimolle, 2005, Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development, Cancer Cell, 7, 313, 10.1016/j.ccr.2005.03.004

Misra, 2015, Zoledronate attenuates accumulation of DNA damage in mesenchymal stem cells and protects their function, Stem Cells (Dayton, Ohio)

Monkkonen, 2006, A new endogenous ATP analog (ApppI) inhibits the mitochondrial adenine nucleotide translocase (ANT) and is responsible for the apoptosis induced by nitrogen-containing bisphosphonates, Br. J. Pharmacol., 147, 437, 10.1038/sj.bjp.0706628

Naidoo, 2016, KRAS-mutant lung cancers in the era of targeted therapy, Adv. Exp. Med. Biol., 893, 155, 10.1007/978-3-319-24223-1_8

Novelli, 2012, Protein farnesylation and disease, J. Inherit. Metab. Dis., 35, 917, 10.1007/s10545-011-9445-y

Panini, 1989, Sterol-independent regulation of 3-hydroxy-3-methylglutaryl-Coa reductase by mevalonate in Chinese-Hamster ovary cells—magnitude and specificity, J. Biol. Chem., 264, 11044, 10.1016/S0021-9258(18)60424-7

Papapoulos, 2008, Bisphosphonates: how do they work?, Best Pract. Res. Clin. Endocrinol. Metab., 22, 831, 10.1016/j.beem.2008.07.001

Paterson, 1990, Microinjection of recombinant p21rho induces rapid changes in cell morphology, J. Cell Biol., 111, 1001, 10.1083/jcb.111.3.1001

Perona, 1997, Activation of the nuclear factor-kappa B by Rho, CDC42, and Rac-1 proteins, Genes Dev., 11, 463, 10.1101/gad.11.4.463

Peterson, 2006, A novel protein geranylgeranyltransferase-I inhibitor with high potency, selectivity, and cellular activity, J. Biol. Chem., 281, 12445, 10.1074/jbc.M600168200

Philips, 2007, Geranylgeranyltransferase I as a target for anti-cancer drugs, J. Clin. Investig., 117, 1223, 10.1172/JCI32108

Piccolo, 2013, Molecular pathways: YAP and TAZ take center stage in organ growth and tumorigenesis, Clin. Cancer Res., 19, 4925, 10.1158/1078-0432.CCR-12-3172

Piccolo, 2014, The biology of YAP/TAZ: hippo signaling and beyond, Physiol. Rev., 94, 1287, 10.1152/physrev.00005.2014

Pich, 2013, Statins reduce melanoma development and metastasis through MICA overexpression, Front. Immunol., 4, 62, 10.3389/fimmu.2013.00062

Pille, 2005, Anti-RhoA and anti-RhoC siRNAs inhibit the proliferation and invasiveness of MDA-MB-231 breast cancer cells in vitro and in vivo, Mol. Ther., 11, 267, 10.1016/j.ymthe.2004.08.029

Ramos, 2012, The Hippo signaling pathway and stem cell biology, Trends Cell Biol., 22, 339, 10.1016/j.tcb.2012.04.006

Rao, 1998, Lovastatin mediated G1 arrest in normal and tumor breast cells is through inhibition of CDK2 activity and redistribution of p21 and p27, independent of p53, Oncogene, 17, 2393, 10.1038/sj.onc.1202322

Reya, 2001, Stem cells, cancer, and cancer stem cells, Nature, 414, 105, 10.1038/35102167

Ridley, 1992, The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors, Cell, 70, 389, 10.1016/0092-8674(92)90163-7

Ridley, 2004, Rho proteins and cancer, Breast Cancer Res. Treat., 84, 13, 10.1023/B:BREA.0000018423.47497.c6

Rollano Penaloza, 2014, Apoptins: selective anticancer agents, Trends Mol. Med., 20, 519, 10.1016/j.molmed.2014.07.003

Roskoski, 2003, Protein prenylation: a pivotal posttranslational process, Biochem. Biophys. Res. Commun., 303, 1, 10.1016/S0006-291X(03)00323-1

Sahai, 2002, RHO-GTPases and cancer, Nat. Rev. Cancer, 2, 133, 10.1038/nrc725

Sane, 2010, A novel geranylgeranyl transferase inhibitor in combination with lovastatin inhibits proliferation and induces autophagy in STS-26T MPNST cells, J. Pharmacol. Exp. Ther., 333, 23, 10.1124/jpet.109.160192

Sasaki, 1998, The Rho small G protein family Rho GDI system as a temporal and spatial determinant for cytoskeletal control, Biochem. Biophys. Res. Commun., 245, 641, 10.1006/bbrc.1998.8253

Schaefer, 2004, Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects, Am. J. Cardiol., 93, 31, 10.1016/j.amjcard.2003.09.008

Scheffzek, 1997, The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants, Science, 277, 333, 10.1126/science.277.5324.333

Sebti, 2005, Protein farnesylation: implications for normal physiology, malignant transformation, and cancer therapy, Cancer Cell, 7, 297, 10.1016/j.ccr.2005.04.005

Shepherd, 2006, Who should receive a statin these days? Lessons from recent clinical trials, J. Intern. Med., 260, 305, 10.1111/j.1365-2796.2006.01700.x

Simons, 2001, Cholesterol and Alzheimer's disease: is there a link?, Neurology, 57, 1089, 10.1212/WNL.57.6.1089

Singh, 2013, Cholesterol biosynthesis and homeostasis in regulation of the cell cycle, PLoS ONE, 8, e58833, 10.1371/journal.pone.0058833

Sjogren, 2007, GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer, J. Clin. Investig., 117, 1294, 10.1172/JCI30868

Smith, 2004, Molecular genetics methods for human intermediate filament diseases, Method Cell Biol., 78, 131, 10.1016/S0091-679X(04)78006-1

Sorrentino, 2014, Metabolic control of YAP and TAZ by the mevalonate pathway, Nat. Cell Biol., 16, 357, 10.1038/ncb2936

Swanson, 2006, Anti-cancer therapy: targeting the mevalonate pathway, Curr. Cancer Drug Targets, 6, 15, 10.2174/156800906775471743

Tardoski, 2015, Low-intensity continuous ultrasound triggers effective bisphosphonate anticancer activity in breast cancer, Sci. Rep., 5, 16354, 10.1038/srep16354

Taylor, 2015, Microenvironment acidity as a major determinant of tumor chemoresistance: proton pump inhibitors (PPIs) as a novel therapeutic approach, Drug Resist. Updates, 23, 69, 10.1016/j.drup.2015.08.004

Taylor, 2012, Joint societies CVD Prevention Guidelines launched in May 2012, Eur. Heart J., 33, 1539

Van Acker, 2016, Bisphosphonates for cancer treatment: mechanisms of action and lessons from clinical trials, Pharmacol. Ther., 158, 24, 10.1016/j.pharmthera.2015.11.008

van Beek, 2003, Differentiating the mechanisms of antiresorptive action of nitrogen containing bisphosphonates, Bone, 33, 805, 10.1016/j.bone.2003.07.007

Veeman, 2003, A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling, Dev. Cell, 5, 367, 10.1016/S1534-5807(03)00266-1

Vega, 2008, Rho GTPases in cancer cell biology, FEBS Lett., 582, 2093, 10.1016/j.febslet.2008.04.039

Vincan, 2007, Frizzled-7 dictates three-dimensional organization of colorectal cancer cell carcinoids, Oncogene, 26, 2340, 10.1038/sj.onc.1210026

Vogt, 1997, The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21WAF1/CIP1/SDI1 in a p53-independent manner, J. Biol. Chem., 272, 27224, 10.1074/jbc.272.43.27224

Wakchoure, 2006, Bisphosphonates inhibit the growth of mesothelioma cells in vitro and in vivo, Clin. Cancer Res., 12, 2862, 10.1158/1078-0432.CCR-05-2766

Wang, 2014, Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility, Proc. Natl. Acad. Sci. U.S.A., 111, E89, 10.1073/pnas.1319190110

Wasik, 2014, Reprogramming and carcinogenesis—parallels and distinctions, Int. Rev. Cell Mol. Biol., 308, 167, 10.1016/B978-0-12-800097-7.00005-1

Weis, 2002, Statins have biphasic effects on angiogenesis, Circulation, 105, 739, 10.1161/hc0602.103393

Whyte, 1997, K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors, J. Biol. Chem., 272, 14459, 10.1074/jbc.272.22.14459

Wojtuszkiewicz, 2016, Folylpolyglutamate synthetase splicing alterations in acute lymphoblastic leukemia are provoked by methotrexate and other chemotherapeutics and mediate chemoresistance, J. Int. Cancer, 138, 1645, 10.1002/ijc.29919

Wolozin, 2000, Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors, Arch. Neurol., 57, 1439, 10.1001/archneur.57.10.1439

Yang, 2000, Protein farnesylation is critical for maintaining normal cell morphology and canavanine resistance in Schizosaccharomyces pombe, J. Biol. Chem., 275, 429, 10.1074/jbc.275.1.429

Yeganeh, 2014, Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease, Pharmacol. Ther., 143, 87, 10.1016/j.pharmthera.2014.02.007

Yoon, 2011, The small GTPase Rac1 is involved in the maintenance of stemness and malignancies in glioma stem-like cells, FEBS Lett., 585, 2331, 10.1016/j.febslet.2011.05.070

Zeman, 1997, Social-contextual influences on expectancies for managing anger and sadness: the transition from middle childhood to adolescence, Dev. Psychol., 33, 917, 10.1037/0012-1649.33.6.917

Zhang, 1996, Protein prenylation: molecular mechanisms and functional consequences, Annu. Rev. Biochem., 65, 241, 10.1146/annurev.bi.65.070196.001325

Zhang, 1995, Rho-family Gtpases regulate P38 mitogen-activated protein-kinase through the downstream mediator Pak1, J. Biol. Chem., 270, 23934, 10.1074/jbc.270.41.23934

Zhao, 2015, Dosing of zoledronic acid with its anti-tumor effects in breast cancer, J. Bone Oncol., 4, 98, 10.1016/j.jbo.2015.08.001

Zhitomirsky, 2016, Lysosomes as mediators of drug resistance in cancer, Drug Resist. Updates, 24, 23, 10.1016/j.drup.2015.11.004