Molecular bases of Sorcin-dependent resistance to chemotherapeutic agents

Abstract

Soluble resistance-related calcium binding protein (Sorcin) is a protein initially labelled “resistance-related”, since it is co-amplified with ABCB1 in multidrug (MD)-resistant cells. While for years Sorcin overproduction was believed to be a by-product of the co-amplification of its gene with the P-glycoprotein gene, many recent studies view Sorcin as an oncoprotein, playing an important role in MD resistance (MDR). Sorcin is one of the most highly expressed calcium-binding proteins, which is overexpressed in many human tumors and MD resistant cancers, and represents a novel MDR marker. Sorcin expression in tumors inversely correlates with patients’ response to chemotherapies and overall prognosis. Sorcin is highly expressed in MDR cell lines over their parent cells. Sorcin overexpression by gene transfection increases drug resistance to a variety of chemotherapeutic drugs in many cancer lines. On the other hand, Sorcin silencing leads to reversal of drug resistance in many cell lines. This review describes: (1) the roles of Sorcin in the cell; (2) the studies showing Sorcin overexpression in tumors and cancer cells; (3) the studies showing the effects of Sorcin overexpression and silencing; (4) the molecular effects of Sorcin overexpression; and (5) the structural and genetic bases of Sorcin-dependent MDR.

Keywords

Sorcin / calcium / cancer / multidrug resistance in cancer / doxorubicin / endoplasmic reticulum / heart / brain / ryanodine receptors / ER stress

References

[1] Van der Bliek AM,Biedler JL,Borst P.A 22-kd protein (sorcin/V19) encoded by an amplified gene in multidrug-resistant cells, is homologous to the calcium-binding light chain of calpain.EMBO J1986;5:3201-8 PMCID:PMC1167313

[2] Colotti G,Fiorillo A,Chiarini V.Sorcin, a calcium binding protein involved in the multidrug resistance mechanisms in cancer cells.Molecules2014;19:13976-89

[3] Hansen C,la Cour JM,Berchtold MW.The PEF family proteins sorcin and grancalcin interact in vivo and in vitro.FEBS Lett2003;545:151-4

[4] Maki M,Satoh H,Shibata H.Structures, functions and molecular evolution of the penta-EF-hand Ca2+-binding proteins.Biochim Biophys Acta2002;1600:51-60

[5] Ilari A,Poser E,Sundell GN,Genovese I.Structural basis of Sorcin-mediated calcium-dependent signal transduction.Sci Rep2015;5:16828 PMCID:PMC4649501

[6] Ilari A,Nastopoulos V,Zamparelli C,Tsernoglou D.The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein.J Mol Biol2002;317:447-58

[7] Colotti G,Verzili D,Loughrey CM,Chiancone E.The W105G and W99G sorcin mutants demonstrate the role of the D helix in the Ca(2+)-dependent interaction with annexin VII and the cardiac ryanodine receptor.Biochemistry2006;45:12519-29

[8] Mella M,Zamparelli C,Ilari A.Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants.J Biol Chem2003;278:24921-8

[9] Zamparelli C,Verzili D,Colotti G,Chiancone E.Structure-function relationships in sorcin, a member of the penta EF-hand family. Interaction of sorcin fragments with the ryanodine receptor and an Escherichia coli model system.Biochemistry2000;39:658-66

[10] Lalioti VS,O'Connell DJ,Sandoval IV.Sorcin links calcium signaling to vesicle trafficking, regulates Polo-like kinase 1 and is necessary for mitosis.PLoS One2014;9:e85438 PMCID:PMC3888430

[11] Maddalena F,Lettini G,Matassa DS,Amoroso MR,Esposito F.Resistance to paclitxel in breast carcinoma cells requires a quality control of mitochondrial antiapoptotic proteins by TRAP1.Mol Oncol2013;7:895-906 PMCID:PMC5528458

[12] Clapham DE.Calcium signaling.Cell2007;131:1047-58

[13] Fowler MR,Chiancone E,Seidler T.Complex modulation of L-type Ca(2+) current inactivation by sorcin in isolated rabbit cardiomyocytes.Pflugers Arch2009;457:1049-60

[14] Fowler MR,Chiancone E,Fearon IM.Sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit in rabbits.Exp Physiol2008;93:1233-8

[15] Franceschini S,Verzili D,Antaramian A,Valdivia HH,Colotti G.Molecular basis for the impaired function of the natural F112L sorcin mutant: X-ray crystal structure, calcium affinity, and interaction with annexin VII and the ryanodine receptor.FASEB J2008;22:295-306

[16] Matsumoto T,Ohkusa T,Sato T,Ikeda Y.Sorcin interacts with sarcoplasmic reticulum Ca(2+)-ATPase and modulates excitation-contraction coupling in the heart.Basic Res Cardiol2005;100:250-62

[17] Meyers MB,Sun YJ,Rohacs T,Zhou YY,Altschuld RA,Coetzee WA.Sorcin regulates excitation-contraction coupling in the heart.J Biol Chem2003;278:28865-71

[18] Suarez J,Scott BT,Wang H,Dillmann WH.Sorcin modulates mitochondrial Ca(2+) handling and reduces apoptosis in neonatal rat cardiac myocytes.Am J Physiol Cell Physiol2013;304:C248-56 PMCID:PMC3566440

[19] Zamparelli C,Colotti G,Seidler T,Chiancone E.Activation of the cardiac Na(+)-Ca(2+) exchanger by sorcin via the interaction of the respective Ca(2+)-binding domains.J Mol Cell Cardiol2010;49:132-41 PMCID:PMC2958309

[20] Marmugi A,Chen X,Hardy J,Marchetti P,Bosco D,Shapiro JA,Magnan C,Thorens B,Rutter GA.Sorcin links pancreatic β-cell lipotoxicity to ER Ca2+ stores.Diabetes2016;65:1009-21 PMCID:PMC4806657

[21] Noordeen NA,Rutter GA.Glucose-induced nuclear shuttling of ChREBP is mediated by sorcin and Ca(2+) ions in pancreatic beta-cells.Diabetes2012;61:574-85 PMCID:PMC3282809

[22] Hu Y,Li S,Wang J,Yang M.Inhibition of sorcin reverses multidrug resistance of K562/A02 cells and MCF-7/A02 cells via regulating apoptosis-related proteins.Cancer Chemother Pharmacol2013;72:789-98

[23] Anthony DF,Paul A.Interaction of calcium/calmodulin-dependent protein kinase IIdeltaC with sorcin indirectly modulates ryanodine receptor function in cardiac myocytes.J Mol Cell Cardiol2007;43:492-503

[24] Salzer U,Hunger U,Prohaska R.Ca(++)-dependent vesicle release from erythrocytes involves stomatin-specific lipid rafts, synexin (annexin VII), and sorcin.Blood2002;99:2569-77

[25] Brownawell AM.Creutz, Calcium-dependent binding of sorcin to the N-terminal domain of synexin (annexin VII).J Biol Chem1997;272:22182-90

[26] Tomas A,Moss SE.Moss, Annexin 11 is required for midbody formation and completion of the terminal phase of cytokinesis.J Cell Biol2004;165:813-22 PMCID:PMC2172404

[27] Lai RC,Lim SK.Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease.Regen Med2011;6:481-92

[28] Buschow SI,Aalberts M,Wauben M.MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.Immunol Cell Biol2010;88:851-6

[29] Demory Beckler M,Franklin JL,Halvey PJ,Whitwell C,Liebler DC.Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.Mol Cell Proteomics2013;12:343-55 PMCID:PMC3567858

[30] Gonzales PA,Hoffert JD,Star RA,Wang NS.Large-scale proteomics and phosphoproteomics of urinary exosomes.J Am Soc Nephrol2009;20:363-79 PMCID:PMC2637050

[31] Keerthikumar S,Liem M,Atukorala I,Mechler A,Ang CS.Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes.Oncotarget2015;6:15375-96 PMCID:PMC4558158

[32] Kharaziha P,Rutishauser D,Lennartsson L,Azimi A,Zubarev R,Yachnin J,Panaretakis T.Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.Oncotarget2015;6:21740-54 PMCID:PMC4673300

[33] Liang B,Chen S,Zhang M,Yang J,Gui T,Shen K.Characterization and proteomic analysis of ovarian cancer-derived exosomes.J Proteomics2013;80:171-82

[34] Pienimaeki-Roemer A,Böttcher A,Black A,Liebisch G,Eisenacher M,Schmitz G.Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets.Transfusion2015;55:507-21

[35] Pisitkun T,Knepper MA.Identification and proteomic profiling of exosomes in human urine.Proc Natl Acad Sci U S A2004;101:13368-73 PMCID:PMC516573

[36] Ali R,Maher SE,Giordano FJ,Geirsson A.miR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling.J Mol Cell Cardiol2012;52:1027-37

[37] Bers DM,Bossuyt J.Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes.Ann N Y Acad Sci2006;1080:165-77

[38] Seidler T,Loughrey CM,Burow A,Teucher N,Kögler H,Hasenfuss G.Effects of adenovirus-mediated sorcin overexpression on excitation-contraction coupling in isolated rabbit cardiomyocytes.Circ Res2003;93:132-9

[39] Lokuta AJ,Sander PR,Valdivia HH.Modulation of cardiac ryanodine receptors by sorcin.J Biol Chem1997;272:25333-8

[40] Collis LP,Zhang J,Sobie EA,Fishman GI.Expression of a sorcin missense mutation in the heart modulates excitation-contraction coupling.FASEB J2007;21:475-87

[41] Farrell EF,Rueda A,Valdivia HH.Sorcin inhibits calcium release and modulates excitation-contraction coupling in the heart.J Biol Chem2003;278:34660-6

[42] Frank KF,Ding Z,Hattebuhr N,Brixius K,Schrader J.Overexpression of sorcin enhances cardiac contractility in vivo and in vitro.J Mol Cell Cardiol2005;38:607-15

[43] Suarez J,Gloss B,McDonough PM,Brunton LL.In vivo adenoviral transfer of sorcin reverses cardiac contractile abnormalities of diabetic cardiomyopathy.Am J Physiol Heart Circ Physiol2004;286:H68-75

[44] Chen X,Farrell ET,Zhao YT,Valdivia HH.Sorcin ablation plus beta-adrenergic stimulation generate an arrhythmogenic substrate in mouse ventricular myocytes.J Mol Cell Cardiol2018;114:199-210

[45] Alzheimer's Association Calcium Hypothesis Workgroup.Calcium hypothesis of Alzheimer's disease and brain aging: a framework for integrating new evidence into a comprehensive theory of pathogenesis.Alzheimers Dement2017;13:178-182.e17

[46] Surmeier DJ,Simuni T.Calcium, mitochondrial dysfunction and slowing the progression of Parkinson's disease.Exp Neurol2017;298:202-9

[47] Del Prete D,Chami M.Ryanodine receptors: physiological function and deregulation in Alzheimer disease.Mol Neurodegener2014;9:21 PMCID:PMC4063224

[48] Pack-Chung E,Pettingell WP,Brownawell AM,Tanzi RE.Presenilin 2 interacts with sorcin, a modulator of the ryanodine receptor.J Biol Chem2000;275:14440-5

[49] Woods WS,Zhou DH,Hartman KL,Qi Z,George JM.Conformation-specific binding of alpha-synuclein to novel protein partners detected by phage display and NMR spectroscopy.J Biol Chem2007;282:34555-67

[50] Tu H,Bezprozvanny A,Lee SF,Serneels L,Yu G.Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations.Cell2006;126:981-93 PMCID:PMC3241869

[51] Takeda T,Yamaguchi O,Nakayama H,Kawai M,Higuchi Y,Watanabe T,Nakai A,Kurihara S,Bernstein A,Iwatsubo T,Otsu K.Presenilin 2 regulates the systolic function of heart by modulating Ca2+ signaling.FASEB J2005;19:2069-71

[52] Kim SI,Kim SS,Chun W.Sequestration of sorcin by aberrant forms of tau results in the defective calcium homeostasis.Korean J Physiol Pharmacol2016;20:387-97 PMCID:PMC4930907

[53] Xie H,Hu X,Tian M,Jiang H,Dong Z,Hu L.Proteomics analysis of MPP+-induced apoptosis in SH-SY5Y cells.Neurol Sci2011;32:221-8

[54] Werner CJ,Mall G.Proteome analysis of human substantia nigra in Parkinson's disease.Proteome Sci2008;6:8 PMCID:PMC2265686

[55] Jin J,Wang Y,Pan C,Zhang J.Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease.Mol Cell Proteomics2006;5:1193-204

[56] Andreev VP,Brewer HM,Xie F,Camp D,Lieberman AP,Nawaz Z,Myers AJ.Label-free quantitative LC-MS proteomics of Alzheimer's disease and normally aged human brains.J Proteome Res2012;11:3053-67 PMCID:PMC3445701

[57] Musunuri S,Ingelsson M,Artemenko K,Kultima K.Quantification of the brain proteome in Alzheimer's disease using multiplexed mass spectrometry.J Proteome Res2014;13:2056-68

[58] Seyfried NT,Swarup V,Duong DM,Deng Q,Hales CM,Glass J,Thambisetty M,Geschwind DH,Levey AI.A multi-network approach identifies protein-specific co-expression in asymptomatic and symptomatic Alzheimer's disease.Cell Syst2017;4:60-72.e4 PMCID:PMC5269514

[59] Drummond E,Faustin A,Hickman RA,Cohen M,Kim C,Shao Y,Ueberheide B.Proteomic differences in amyloid plaques in rapidly progressive and sporadic Alzheimer's disease.Acta Neuropathol2017;133:933-54 PMCID:PMC5503748

[60] Hondius DC,Morrema THJ,van Nierop P,Li KW,Smit AB.Proteomics analysis identifies new markers associated with capillary cerebral amyloid angiopathy in Alzheimer's disease.Acta Neuropathol Commun2018;6:46 PMCID:PMC5985582

[61] Umoh ME,Dai J,Lah JJ,Gearing M,Seyfried NT.A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain.EMBO Mol Med2018;10:48-62 PMCID:PMC5760858

[62] Kalathur RK,Machado S,Ayasolla KR.The unfolded protein response and its potential role in Huntington's disease elucidated by a systems biology approach.Version 2. F1000Res2015;4:103 PMCID:PMC4758378

[63] Gracy KN,Meyers MB.N-methyl-D-aspartate receptor 1 in the caudate-putamen nucleus: ultrastructural localization and co-expression with sorcin, a 22,000 mol.wt calcium binding protein. Neuroscience1999;90:107-17

[64] Clemen CS,Hövelmeyer N.The lack of annexin A7 affects functions of primary astrocytes.Exp Cell Res2003;291:406-14

[65] Meyers MB.Increased synthesis of a low molecular weight protein in vincristine-resistant cells.Biochem Biophys Res Commun1981;99:228-35

[66] Van der Bliek AM,Van der Velde-Koerts T,Meyers MB,Hamilton TC,Borst P.Genes amplified and overexpressed in human multidrug-resistant cell lines.Cancer Res1988;48:5927-32

[67] Deng L,Leng A,Xu M,Gu H.Upregulation of soluble resistance-related calcium-binding protein (sorcin) in gastric cancer.Med Oncol2010;27:1102-8

[68] Padar S,Thomas DW,Livesey JC.Differential regulation of calcium homeostasis in adenocarcinoma cell line A549 and its Taxol-resistant subclone.Br J Pharmacol2004;142:305-16 PMCID:PMC1574945

[69] Qi J,Zhou Y,Cheng Y,Zhu Z.Overexpression of sorcin in multidrug resistant human leukemia cells and its role in regulating cell apoptosis.Biochem Biophys Res Commun2006;349:303-9

[70] Qu Y,Liu B.Comparative proteomic profiling identified sorcin being associated with gemcitabine resistance in non-small cell lung cancer.Med Oncol2010;27:1303-8

[71] Tan Y,Zhao C,Zhao H,Han M.Expression of sorcin predicts poor outcome in acute myeloid leukemia.Leuk Res2003;27:125-31

[72] Yamagishi N,Kondo R,Saito Y,Hatayama T.Increased expression of sorcin is associated with multidrug resistance in leukemia cells via up-regulation of MDR1 expression through cAMP response element-binding protein.Biochem Biophys Res Commun2014;448:430-6

[73] Yang YX,Zhang GY,Xiao ZQ.A subcelluar proteomic investigation into vincristine-resistant gastric cancer cell line.J Cell Biochem2008;104:1010-21

[74] Zhou Y,Tan Y,Xiao Y,Zhu Z.Sorcin, an important gene associated with multidrug-resistance in human leukemia cells.Leuk Res2006;30:469-76

[75] Gao Y,Liu X,Zhao X.Reversing effect and mechanism of soluble resistance-related calcium-binding protein on multidrug resistance in human lung cancer A549/DDP cells.Mol Med Rep2015;11:2118-24

[76] Sun Y,Meng Q,Huo X,Sun H,Peng J.Targeting P-glycoprotein and SORCIN: dihydromyricetin strengthens anti-proliferative efficiency of adriamycin via MAPK/ERK and Ca2+ -mediated apoptosis pathways in MCF-7/ADR and K562/ADR.J Cell Physiol2018;233:3066-79

[77] Dabaghi M,Moshtaghian J,Abedi M.Overexpression of SORCIN is a prognostic biomarker for multidrug-resistant pediatric acute lymphoblastic leukemia and correlates with upregulated MDR1/P-gp.Genet Test Mol Biomarkers2016;20:516-21

[78] Maddalena F,Piscazzi A,Scorziello A,Matassa DS,Neri V,Landriscina M.Sorcin induces a drug-resistant phenotype in human colorectal cancer by modulating Ca(2+) homeostasis.Cancer Res2011;71:7659-69

[79] Tong W,Wang Q.Sorcin enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer.Cell Biochem Biophys2015;72:453-9

[80] Mangia A,Dell'Endice S,Saragoni L,Santini D,Simone G.The potential predictive role of nuclear NHERF1 expression in advanced gastric cancer patients treated with epirubicin/oxaliplatin/capecitabine first line chemotherapy.Cancer Biol Ther2015;16:1140-7 PMCID:PMC4622862

[81] Xu P,Wang JH.shRNA-mediated silencing of sorcin increases drug chemosensitivity in myeloma KM3/DDP and U266/ADM cell lines.Int J Clin Exp Pathol2015;8:2300-10 PMCID:PMC4440046

[82] Pomeroy SL,Gaasenbeek M,Angelo M,Kim JY,Black PM,Allen JC,Olson JM,Wetmore C,Poggio T,Rifkin R,Stolovitzky G,Mesirov JP,Golub TR.Prediction of central nervous system embryonal tumour outcome based on gene expression.Nature2002;415:436-42

[83] French PJ,Nagel JH,Brouwer E,Luider TM,van den Bent MJ.Gene expression profiles associated with treatment response in oligodendrogliomas.Cancer Res2005;65:11335-44

[84] Shai R,Kremen TJ,Liau LM,Mischel PS.Gene expression profiling identifies molecular subtypes of gliomas.Oncogene2003;22:4918-23

[85] Sun L,Su Q,Kotliarov Y,Passaniti A,Walling J,Rosenblum M,Fine HA.Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain.Cancer Cell2006;9:287-300

[86] Yokota T,Adachi K,Teramoto A,Sugisaki Y,Tsunoda T.Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin.Acta Neuropathol2006;111:29-38

[87] Genovese I,Ilari A,Fazi F.Binding of doxorubicin to Sorcin impairs cell death and increases drug resistance in cancer cells.Cell Death Dis2017;8:e2950 PMCID:PMC5550883

[88] Hamada H,Oh-hara T.Purification of the Mr 22,000 calcium-binding protein (sorcin) associated with multidrug resistance and its detection with monoclonal antibodies.Cancer Res1988;48:3173-8

[89] He Q,Hou D,Xu M,Liu T.Overexpression of sorcin results in multidrug resistance in gastric cancer cells with up-regulation of P-gp.Oncol Rep2011;25:237-43

[90] Kawakami M,Okamura N,Markova S,Hashimoto N,Sakaeda T.Knock-down of sorcin induces up-regulation of MDR1 in HeLa cells.Biol Pharm Bull2007;30:1065-73

[91] Liu X,Feng B.Reversing effect of sorcin in the drug resistance of human nasopharyngeal carcinoma.Anat Rec (Hoboken)2014;297:215-21

[92] Parekh HK,Choudhary K,Simpkins H.Overexpression of sorcin, a calcium-binding protein, induces a low level of paclitaxel resistance in human ovarian and breast cancer cells.Biochem Pharmacol2002;63:1149-58

[93] Gong Z,Chu H,Sun D.Overexpression of sorcin in multidrug-resistant human breast cancer.Oncol Lett2014;8:2393-8 PMCID:PMC4214497

[94] Hu Y,Yang M,Fan D,Zhang Y,Xiong D.Sorcin silencing inhibits epithelial-to-mesenchymal transition and suppresses breast cancer metastasis in vivo.Breast Cancer Res Treat2014;143:287-99

[95] Tuo H,She S,Zou XQ,Hu HD,Ren H,Yang YX.Sorcin induces gastric cancer cell migration and invasion contributing to STAT3 activation.Oncotarget2017;8:104258-71 PMCID:PMC5732804

[96] Li X,Wang Y,Li X,Gao X.Negative regulation of hepatic inflammation by the soluble resistance-related calcium-binding protein via signal transducer and activator of transcription 3.Front Immunol2017;8:709

[97] Lei X,Chen J,Lei J,Duanmu J,Liu D,Li T.Sorcin predicts poor prognosis and promotes metastasis by facilitating epithelial-mesenchymal transition in hepatocellular carcinoma.Sci Rep2017;7:10049 PMCID:PMC5577205

[98] Gupta K,Kumari S,Manohar M,Dwivedi A.Sorcin is involved during embryo implantation via activating VEGF/PI3K/Akt pathway in mice.J Mol Endocrinol2018;60:119-132

[99] Li GY,Liu JZ,Xiao TW,Wang JX,Hou M.Marine drug Haishengsu increases chemosensitivity to conventional chemotherapy and improves quality of life in patients with acute leukemia.Biomed Pharmacother2016;81:160-5

[100] Sun Y,Meng Q,Huo X,Sun H,Peng J.Targeting P-glycoprotein and SORCIN: Dihydromyricetin strengthens anti-proliferative efficiency of adriamycin via MAPK/ERK and Ca(2+) -mediated apoptosis pathways in MCF-7/ADR and K562/ADR.J Cell Physiol2018;233:3066-79

[101] Li GY,Zhang B,Chen SG,Wang LX.Tegillarca granosa extract Haishengsu (HSS) suppresses expression of mdr1, BCR/ABL and sorcin in drug-resistant K562/ADM tumors in mice.Adv Med Sci2013;58:112-7

[102] Callen DF,Simmers RN,Roninson IB.Localization of the human multiple drug resistance gene, MDR1, to 7q21.1.Hum Genet1987;77:142-4

[103] Fojo AT,Slamon DJ,Gottesman MM.Expression of a multidrug-resistance gene in human tumors and tissues.Proc Natl Acad Sci U S A1987;84:265-9 PMCID:PMC304184

[104] Schoenlein PV.Molecular cytogenetics of multiple drug resistance.Cytotechnology1993;12:63-89

[105] Scotto KW,Melera PW.Amplification and expression of genes associated with multidrug resistance in mammalian cells.Science1986;232:751-5

[106] Van der Bliek AM,Ling V.Overexpression and amplification of five genes in a multidrug-resistant Chinese hamster ovary cell line.Mol Cell Biol1986;6:1671-8 PMCID:PMC367694

[107] Abolhoda A,Ross H,Burt M.Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin.Clin Cancer Res1999;5:3352-6

[108] Atalay C,Irkkan C.Multidrug resistance in locally advanced breast cancer..Tumour Biol2006;27:309-18

[109] Brügger D,Liu C,Niethammer D,Beck JF.Induction of drug resistance and protein kinase C genes in A2780 ovarian cancer cells after incubation with antineoplastic agents at sublethal concentrations.Anticancer Res2002;22:4229-32

[110] Chin KV,Darlington G,Gottesman MM.Heat shock and arsenite increase expression of the multidrug resistance (MDR1) gene in human renal carcinoma cells.J Biol Chem1990;265:221-6

[111] Gekeler V,Diddens H.Expression of a P-glycoprotein gene is inducible in a multidrug-resistant human leukemia cell line.Biochem Biophys Res Commun1988;155:754-60

[112] Hu XF,Wall DM,Parkin JD,Zalcberg JR.Rapid up-regulation of mdr1 expression by anthracyclines in a classical multidrug-resistant cell line.Br J Cancer1995;71:931-6

[113] Liu ZL,Tanaka S,Hirano T.Induction of multidrug resistance in MOLT-4 cells by anticancer agents is closely related to increased expression of functional P-glycoprotein and MDR1 mRNA.Cancer Chemother Pharmacol2002;49:391-7

[114] Park J,Liebert M,Flint A.P-glycoprotein expression in bladder cancer.J Urol1994;151:43-6

[115] Schneider J,Centeno MM,Rodríguez-Escudero FJ.High rate of expression of multidrug resistance-associated P-glycoprotein in human endometrial carcinoma and normal endometrial tissue.Eur J Cancer1993;29A:554-8

[116] Flahaut M,Martinet D,Bourloud KB,Meier R,Delattre O,Gross N.Molecular cytogenetic characterization of doxorubicin-resistant neuroblastoma cell lines: evidence that acquired multidrug resistance results from a unique large amplification of the 7q21 region.Genes Chromosomes Cancer2006;45:495-508

[117] Kitada K.The MDR1/ABCB1 regional amplification in large inverted repeats with asymmetric sequences and microhomologies at the junction sites.Cancer Genet Cytogenet2007;178:120-7

[118] Kadioglu O.Peptide aptamer identified by molecular docking targeting translationally controlled tumor protein in leukemia cells.Invest New Drugs2016;34:515-21

[119] Chen GK,Durán GE,Bangs CD,Kovacs M,Brown JM.Preferential expression of a mutant allele of the amplified MDR1 (ABCB1) gene in drug-resistant variants of a human sarcoma.Genes Chromosomes Cancer2002;34:372-83

[120] Duesberg P,Sachs R,Upender MB.Cancer drug resistance: the central role of the karyotype.Drug Resist Updat2007;10:51-8

[121] Katoh H,Kokubu A,Loukopoulos P,Kosuge T,Kondo T,Hosoda F,Imoto I,Hirohashi S.Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: identification of genetic indicators to predict patient outcome.J Hepatol2005;43:863-74

[122] Mickley LA,Knutsen TA,Fojo T.Gene rearrangement: a novel mechanism for MDR-1 gene activation.J Clin Invest1997;99:1947-57 PMCID:PMC508019

[123] Pang E,Chan KY,Squire JA,Beheshti B,Leung TW.Karyotypic imbalances and differential gene expressions in the acquired doxorubicin resistance of hepatocellular carcinoma cells.Lab Invest2005;85:664-74

[124] Kim IW,Kim MG,Oh JM.Copy number variability analysis of pharmacogenes in patients with lymphoma, leukemia, hepatocellular, and lung carcinoma using the cancer genome Atlas data.Pharmacogenet Genomics2015;25:1-7

[125] Bonte D,Liu H,Furge K.Cdc7-Dbf4 kinase overexpression in multiple cancers and tumor cell lines is correlated with p53 inactivation.Neoplasia2008;10:920-31 PMCID:PMC2517636

[126] Chao CC,Lin-Chao S.Co-amplification and over-expression of two mdr genes in a multidrug-resistant human colon carcinoma cell line.FEBS Lett1991;291:214-8

[127] Cheng AN,Fan CC,Kuo CY,Liu YL,Chen WS,Wang TY.Increased Cdc7 expression is a marker of oral squamous cell carcinoma and overexpression of Cdc7 contributes to the resistance to DNA-damaging agents.Cancer Lett2013;337:218-25

[128] Finalet Ferreiro J,Urbankova H,Michaux L,Krenacs L,De Paepe P,Verhoef G,Vandenberghe P,Wlodarska I.Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma.PLoS One2014;9:e102977 PMCID:PMC4109958

[129] Hansen SN,Zhu S,Nielsen RL,Wang G,Zhang X,Bolund L,Wang J,Ditzel HJ,Schrohl AS,Gupta R.The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells.BMC Genomics2016;17:442 PMCID:PMC4899892

[130] Litviakov NV,Tsyganov MM,Ibragimova MK,Kzhyshkowska J.Deletions of multidrug resistance gene loci in breast cancer leads to the down-regulation of its expression and predict tumor response to neoadjuvant chemotherapy.Oncotarget2016;7:7829-41 PMCID:PMC4884957

[131] Patch AM,Etemadmoghadam D,George J,Nones K,Alsop K,Kassahn KS,Quinn MC,Quek K,Curry E,Australian Ovarian Cancer Study Group,Mileshkin L,Kennedy C,Chiew YE,Friedlander M,Pyman J,O'Brien P,Young G,Waring P,Mitchell C,Hendley J,Shackleton M,Arnau GM,Holloway TP,Harliwong I,Nourbakhsh E,Idrisoglu S,Christ AN,Holmes O,Leonard C,Hall N,Taylor DF,Fink JL,Drapkin R,Gabra H,Jewell A,Markham E,Ellul J,Doyle MA,Stewart C,Pearson JV,deFazio A,Bowtell DD.Whole-genome characterization of chemoresistant ovarian cancer.Nature2015;521:489-94

[132] Torigoe K,Kusaba H,Kuwano M,Green ED,Scherer SW,Wada M.A YAC-based contig of 1.5 Mb spanning the human multidrug resistance gene region and delineating the amplification unit in three human multidrug-resistant cell lines.Genome Res1995;5:233-44

[133] Yabuki N,Yamasaki T,Mio T,Fujii T.Gene amplification and expression in lung cancer cells with acquired paclitaxel resistance.Cancer Genet Cytogenet2007;173:1-9

[134] Januchowski R,Zawierucha P,Świerczewska M,Bednarek-Rajewska K,Nowicki M,Klejewski A.Microarray-based detection and expression analysis of new genes associated with drug resistance in ovarian cancer cell lines.Oncotarget2017;8:49944-58 PMCID:PMC5564819

[135] Lee S,Ho JN,Byun SS.Analysis of resistance-associated gene expression in docetaxel-resistant prostate cancer cells.Oncol Lett2017;14:3011-8 PMCID:PMC5588173

[136] Sasi NK,Lanning NJ,Weinreich M.DDK Promotes Tumor Chemoresistance and Survival via Multiple Pathways.Neoplasia2017;19:439-50 PMCID:PMC5406526

[137] Genovese I,Assaraf YG,Colotti G.Not only P-glycoprotein: amplification of the ABCB1-containing chromosome region 7q21 confers multidrug resistance upon cancer cells by coordinated overexpression of an assortment of resistance-related proteins.Drug Resist Updat2017;32:23-46

[138] Wang YC,Francisco B,Duran GE,Chen X.Regional activation of chromosomal arm 7q with and without gene amplification in taxane-selected human ovarian cancer cell lines.Genes Chromosomes Cancer2006;45:365-74

[139] Yang Y,Hou S,Liu J.The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell.PLoS One2013;8:e65309 PMCID:PMC3669360

[140] Han C,Duan Z.Role of microRNA-1 in human cancer and its therapeutic potentials.Biomed Res Int2014;2014:428371 PMCID:PMC4052501

[141] Kim CH,Rettig RL,Lee ET,Choi IJ,Green JE.miRNA signature associated with outcome of gastric cancer patients following chemotherapy.BMC Med Genomics2011;4:79 PMCID:PMC3287139