Targeting Ca2+ transport in cancer: Close reality or long perspective?

Expert Opinion on Therapeutic Targets

Volumn 17, Issue 3, 2013, Pages 225-241

  Prevarskaya, Natalia ^a   Skryma, Roman ^b   Shuba, Yaroslav ^c,d  

^a Université des Sciences et Technologies de Lille   (France)

^b Laboratory of Excellence Ion Channel Science and Therapeutics   (France)

^c BOGOMOLETZ INSTITUTE OF PHYSIOLOGY   (Ukraine)

^d State Key Laboratory of Molecular and Cellular Biology   (Ukraine)

Author keywords

Angiogenesis; Apoptosis; Autophagy; Ca2+ channels; Ca2+ pumps; Cancer; Migration; Proliferation

Indexed keywords

3,3' DIINDOLYLMETHANE; 5 AMINO 1 [3,5 DICHLORO 4 (4 CHLOROBENZOYL)BENZYL] 1H 1,2,3 TRIAZOLE 4 CARBOXAMIDE; ADENOSINE TRIPHOSPHATASE; ADENOSINE TRIPHOSPHATASE (CALCIUM); ANTIBODY; ANTINEOPLASTIC AGENT; ARTEMISININ; CAFFEINE; CALCIUM ION; CALCIUM MANGANESE TRANSPORTING ADENOSINE TRIPHOSPHATASE; CALOXIN; CARDIAC GLYCOSIDE; CARRIER PROTEIN; CISPLATIN; CP 4071; DIGITOXIN; DIGOXIN; DOXORUBICIN; G 202; G PROTEIN COUPLED RECEPTOR; PLASMA MEMBRANE CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; RYANODINE RECEPTOR; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SMALL INTERFERING RNA; SODIUM CALCIUM EXCHANGE PROTEIN; THAPSIGARGIN; TRANSIENT RECEPTOR POTENTIAL CHANNEL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VISMODEGIB; VOLTAGE DEPENDENT ANION CHANNEL; VOLTAGE GATED CALCIUM CHANNEL;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; AUTOPHAGY; BASAL CELL CARCINOMA; CALCIUM HOMEOSTASIS; CALCIUM MOBILIZATION; CALCIUM SIGNALING; CALCIUM TRANSPORT; CANCER CELL; CANCER DIAGNOSIS; CANCER INHIBITION; CARCINOGENESIS; CELL GROWTH; CELL MIGRATION; CELL PROLIFERATION; CONGESTIVE HEART FAILURE; CYTOTOXICITY; DRUG TARGETING; ENDOPLASMIC RETICULUM; GENE MUTATION; HEART ARRHYTHMIA; HUMAN; MALIGNANT NEOPLASTIC DISEASE; METASTASIS INHIBITION; MOLECULARLY TARGETED THERAPY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHENOTYPE; PROTEIN FUNCTION; REVIEW; SECOND MESSENGER; TUMOR VASCULARIZATION;

ANIMALS; BIOLOGICAL TRANSPORT; CALCIUM; CALCIUM-TRANSPORTING ATPASES; HUMANS; NEOPLASMS;

EID: 84873900703     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2013.741594     Document Type: Review

References (160)

1. World Health Organization media centre, cancer. Available from: http://www.who.int/mediacentre/factsheets/fs297/en/index. html [Last accessed 12 July 2012]
2. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 2000;1(1):11-21
3. Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003;4(7):517-29
4. Allbritton NL, Meyer T. Localized calcium spikes and propagating calcium waves. Cell Calcium 1993;14(10):691-7
5. Bootman MD, Lipp P, Berridge MJ. The organisation and functions of local Ca(2+) signals. J Cell Sci 2001;114(Pt 12):2213-22
6. Lipskaia L, Lompre AM. Alteration in temporal kinetics of Ca2+ signaling and control of growth and proliferation. Biol Cell 2004;96(1):55-68
7. Munaron L, Antoniotti S, Lovisolo D. Intracellular calcium signals and control of cell proliferation: how many mechanisms? J Cell Mol Med 2004;8(2):161-8
8. Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 2003;4(7):552-65
9. Brini M, Carafoli E. Calcium pumps in health and disease. Physiol Rev 2009;89(4):1341-78
10. Monteith GR, Davis FM, Roberts-Thomson SJ. Calcium channels and pumps in cancer: changes and consequences. J Biol Chem 2012;14287(38):31666-73
11. Prasad V, Okunade GW, Miller ML, Shull GE. Phenotypes of SERCA and PMCA knockout mice. Biochem Biophys Res Commun 2004;1322(4):1192-203
12. Hong JH, Yang YM, Kim HS, et al. Markers of squamous cell carcinoma in sarco/endoplasmic reticulum Ca2+ ATPase 2 heterozygote mice keratinocytes. Prog Biophys Mol Biol 2010;103(1):81-7
13. Endo Y, Uzawa K, Mochida Y, et al. Sarcoendoplasmic reticulum Ca(2+) ATPase type 2 downregulated in human oral squamous cell carcinoma. Int J Cancer 2004;10110(2):225-31
14. Korosec B, Glavac D, Volavsek M, et al. ATP2A3 gene is involved in cancer susceptibility. Cancer Genet Cytogenet 2009;15188(2):88-94
15. Arbabian A, Brouland JP, Gelebart P, et al. Endoplasmic reticulum calcium pumps and cancer. Biofactors 2011;37(3):139-49
16. Vanden Abeele F, Skryma R, Shuba Y, et al. Bcl-2-dependent modulation of Ca(2+) homeostasis and store-operated channels in prostate cancer cells. Cancer Cell 2002;1(2):169-79
17. Vanoverberghe K, Vanden Abeele F, Mariot P, et al. Ca2+ homeostasis and apoptotic resistance of neuroendocrine-differentiated prostate cancer cells. Cell Death Differ 2004;11(3):321-30
18. Prevarskaya N, Skryma R, Shuba Y. Ca2+ homeostasis in apoptotic resistance of prostate cancer cells. Biochem Biophys Res Commun 2004;1322(4):1326-35
19. Papp B, Brouland JP, Gelebart P, et al. Endoplasmic reticulum calcium transport ATPase expression during differentiation of colon cancer and leukaemia cells. Biochem Biophys Res Commun 2004;1322(4):1223-36
20. Strehler EE, Filoteo AG, Penniston JT, et al. Plasma-membrane Ca(2+) pumps: structural diversity as the basis for functional versatility. Biochem Soc Trans 2007;35(Pt 5):919-22
21. Roberts-Thomson SJ, Curry MC, Monteith GR. Plasma membrane calcium pumps and their emerging roles in cancer. World J Biol Chem 2010;261(8):248-53
22. Curry MC, Roberts-Thomson SJ, Monteith GR. Plasma membrane calcium ATPases and cancer. Biofactors 2011;37(3):132-8
23. Lee WJ, Roberts-Thomson SJ, Monteith GR. Plasma membrane calcium-ATPase 2 and 4 in human breast cancer cell lines. Biochem Biophys Res Commun 2005;25337(3):779-83
24. VanHouten J, Sullivan C, Bazinet C, et al. PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer. Proc Natl Acad Sci USA 2010;107(25):11405-10
25. Holton M, Yang D, Wang W, et al. The interaction between endogenous calcineurin and the plasma membrane calcium-dependent ATPase is isoform specific in breast cancer cells. FEBS Lett 2007;21581(21):4115-19
26. Aung CS, Ye W, Plowman G, et al. Plasma membrane calcium ATPase 4 and the remodeling of calcium homeostasis in human colon cancer cells. Carcinogenesis 2009;30(11):1962-9
27. Saito K, Uzawa K, Endo Y, et al. Plasma membrane Ca2+ ATPase isoform 1 down-regulated in human oral cancer. Oncol Rep 2006;15(1):49-55
28. Missiaen L, Dode L, Vanoevelen J, et al. Calcium in the Golgi apparatus. Cell Calcium 2007;41(5):405-16
29. Vanoevelen J, Dode L, Raeymaekers L, et al. Diseases involving the Golgi calcium pump. Subcell Biochem 2007;45:385-404
30. Okunade GW, Miller ML, Azhar M, et al. Loss of the Atp2c1 secretory pathway Ca(2+)-ATPase (SPCA1) in mice causes Golgi stress, apoptosis, and midgestational death in homozygous embryos and squamous cell tumors in adult heterozygotes. J Biol Chem 2007;7282(36):26517-27
31. Feng M, Grice DM, Faddy HM, et al. Store-independent activation of Orai1 by SPCA2 in mammary tumors. Cell 2010;1143(1):84-98
32. Grice DM, Vetter I, Faddy HM, et al. Golgi calcium pump secretory pathway calcium ATPase 1 (SPCA1) is a key regulator of insulin-like growth factor receptor (IGF1R) processing in the basal-like breast cancer cell line MDA-MB-231. J Biol Chem 2010;26285(48):37458-66
33. Philipson KD, Nicoll DA. Sodium-calcium exchange: a molecular perspective. Annu Rev Physiol 2000;62:111-33
34. McConkey DJ, Lin Y, Nutt LK, et al. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells. Cancer Res 2000;1560(14):3807-12
35. Newman RA, Yang P, Pawlus AD, et al. Cardiac glycosides as novel cancer therapeutic agents. Mol Interv 2008;8(1):36-49
36. Kim HL, Im DS. N, N-dimethyl-D-erythro-sphingosine increases intracellular Ca2+ concentration via Na+-Ca2+-exchanger in HCT116 human colon cancer cells. Arch Pharm Res 2008;31(1):54-9
37. Dong H, Shim KN, Li JM, et al. Molecular mechanisms underlying Ca2 +-mediated motility of human pancreatic duct cells. Am J Physiol Cell Physiol 2010;299(6):C1493-503
38. Bianchi K, Rimessi A, Prandini A, et al. Calcium and mitochondria: mechanisms and functions of a troubled relationship. Biochim Biophys Acta 2004;61742(1-3):119-31
39. De Stefani D, Raffaello A, Teardo E, et al. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 2011;19476(7360):336-40
40. Baughman JM, Perocchi F, Girgis HS, et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 2011;19476(7360):341-5
41. Wenner CE. Targeting mitochondria as a therapeutic target in cancer. J Cell Physiol 2012;227(2):450-6
42. Catterall WA, Perez-Reyes E, Snutch TP, et al. International union of pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 2005;57(4):411-25
43. Collingridge GL, Olsen RW, Peters J, et al. A nomenclature for ligand-gated ion channels. Neuropharmacology 2009;56(1):2-5
44. Venkatachalam K, Montell C. TRP channels. Annu Rev Biochem 2007;76:387-417
45. Varnai P, Hunyady L, Balla T. STIM and Orai: the long-awaited constituents of store-operated calcium entry. Trends Pharmacol Sci 2009;30(3):118-28
46. Shuttleworth TJ. STIM and Orai proteins and the non-capacitative ARC channels. Front Biosci 2012;117:847-60
47. Prevarskaya N, Zhang L, Barritt G. TRP channels in cancer. Biochim Biophys Acta 2007;1772(8):937-46
48. Prevarskaya N, Skryma R, Shuba Y. Ion channels and the hallmarks of cancer. Trends Mol Med 2010;16(3):107-21
49. Foskett JK, White C, Cheung KH, et al. Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev 2007;87(2):593-658
50. Calcraft PJ, Ruas M, Pan Z, et al. NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 2009;28459(7246):596-600
51. Rah SY, Mushtaq M, Nam TS, et al. Generation of cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate by CD38 for Ca2+ signaling in interleukin-8-treated lymphokine-activated killer cells. J Biol Chem 2010;9285(28):21877-87
52. Lewis RS. Calcium oscillations in T-cells: mechanisms and consequences for gene expression. Biochem Soc Trans 2003;31(Pt 5):925-9
53. Parkash J, Asotra K. Calcium wave signaling in cancer cells. Life Sci 2010;2087(19-22):587-95
54. Wei C, Wang X, Zheng M, et al. Calcium gradients underlying cell migration. Curr Opin Cell Biol 2012;24(2):254-61
55. Chandra S. Quantitative imaging of chemical composition in single cells by secondary ion mass spectrometry: cisplatin affects calcium stores in renal epithelial cells. Methods Mol Biol 2010;656:113-30
56. Kuznetsov AV, Margreiter R, Amberger A, et al. Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death. Biochim Biophys Acta 2011;1813(6):1144-52
57. Roderick HL, Cook SJ. Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival. Nat Rev Cancer 2008;8(5):361-75
58. Becchetti A. Ion channels and transporters in cancer. 1. Ion channels and cell proliferation in cancer. Am J Physiol Cell Physiol 2011;301(2):C255-65
59. Legrand G, Humez S, Slomianny C, et al. Ca2+ pools and cell growth. Evidence for sarcoendoplasmic Ca2+-ATPases 2B involvement in human prostate cancer cell growth control. J Biol Chem 2001;14276(50):47608-14
60. Sakakura C, Hagiwara A, Fukuda K, et al. Possible involvement of inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers. Anticancer Res 2003;23(5A):3691-7
61. Szatkowski C, Parys JB, Ouadid-Ahidouch H, et al. Inositol 1, 4, 5-trisphosphate-induced Ca2+ signalling is involved in estradiol-induced breast cancer epithelial cell growth. Mol Cancer 2010;219:156
62. Motiani RK, Abdullaev IF, Trebak M. A novel native store-operated calcium channel encoded by Orai3: selective requirement of Orai3 versus Orai1 in estrogen receptor-positive versus estrogen receptor-negative breast cancer cells. J Biol Chem 2010; 18285 (25) 19173-83
63. Chen YF, Chiu WT, Chen YT, et al. Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis. Proc Natl Acad Sci USA 2011;108(37):15225-30
64. Hou MF, Kuo HC, Li JH, et al. Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells. Biochim Biophys Acta 2011;1810(12):1278-84
65. Faouzi M, Hague F, Potier M, et al. Down-regulation of Orai3 arrests cell-cycle progression and induces apoptosis in breast cancer cells but not in normal breast epithelial cells. J Cell Physiol 2011;226(2):542-51
66. Liu H, Hughes JD, Rollins S, et al. Calcium entry via ORAI1 regulates glioblastoma cell proliferation and apoptosis. Exp Mol Pathol 2011;91(3):753-60
67. Panner A, Wurster RD. T-type calcium channels and tumor proliferation. Cell Calcium 2006;40(2):253-9
68. Lehen'kyi V, Flourakis M, Skryma R, et al. TRPV6 channel controls prostate cancer cell proliferation via Ca(2+)/NFAT-dependent pathways. Oncogene 2007;1526(52):7380-5
69. Thebault S, Flourakis M, Vanoverberghe K, et al. Differential role of transient receptor potential channels in Ca2+ entry and proliferation of prostate cancer epithelial cells. Cancer Res 2006;1566(4):2038-47
70. Aydar E, Yeo S, Djamgoz M, et al. Abnormal expression, localization and interaction of canonical transient receptor potential ion channels in human breast cancer cell lines and tissues: a potential target for breast cancer diagnosis and therapy. Cancer Cell Int 2009;189:23
71. Wang Y, Yue D, Li K, et al. The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells. Asian J Androl 2010;12(6):841-52
72. Ding X, He Z, Shi Y, et al. Targeting TRPC6 channels in oesophageal carcinoma growth. Expert Opin Ther Targets 2010;14(5):513-27
73. Zeng X, Sikka SC, Huang L, et al. Novel role for the transient receptor potential channel TRPM2 in prostate cancer cell proliferation. Prostate Cancer Prostatic Dis 2010;13(2):195-201
74. Guilbert A, Gautier M, Dhennin-Duthille I, et al. Evidence that TRPM7 is required for breast cancer cell proliferation. Am J Physiol Cell Physiol 2009;297(3):C493-502
75. Yang ZH, Wang XH, Wang HP, et al. Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells. Asian J Androl 2009;11(2):157-65
76. Zhou F, Yang Y, Xing D. Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis. FEBS J 2011;278(3):403-13
77. White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 2012;12(6):401-10
78. Bouillet P, Strasser A. BH3-only proteins-evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 2002;15115(Pt 8):1567-74
79. Høyer-Hansen M, Jaattela M. Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ 2007;14(9):1576-82
80. Rao RV, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 2004;11(4):372-80
81. McConkey DJ, Orrenius S. The role of calcium in the regulation of apoptosis. Biochem Biophys Res Commun 1997;20239(2):357-66
82. Flourakis M, Lehen'kyi V, Beck B, et al. Orai1 contributes to the establishment of an apoptosis-resistant phenotype in prostate cancer cells. Cell Death Dis 2010;161:e75
83. Berry PA, Birnie R, Droop AP, et al. The calcium sensor STIM1 is regulated by androgens in prostate stromal cells. Prostate 2011;71(15):1646-55
84. Zhu N, Pewitt EB, Cai X, et al. Calreticulin: an intracellular Ca+ +-binding protein abundantly expressed and regulated by androgen in prostatic epithelial cells. Endocrinology 1998;139(10):4337-44
85. Ghantous A, Gali-Muhtasib H, Vuorela H, et al. What made sesquiterpene lactones reach cancer clinical trials? Drug Discov Today 2010;15(15-16):668-78
86. Denmeade SR, Isaacs JT. The SERCA pump as a therapeutic target: making a "smart bomb" for prostate cancer. Cancer Biol Ther 2005;4(1):14-22
87. Clinical Trials database search results. Available from: http://clinicaltrials.gov/ct2/results?term=G-202 [Last accessed 12 July 2012]
88. Stenkvist B. Is digitalis a therapy for breast carcinoma? Oncol Rep 1999;6(3):493-6
89. Zhang H, Qian DZ, Tan YS, et al. Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci USA 2008;105(50):19579-86
90. Lin J, Carducci MA. HIF-1alpha inhibition as a novel mechanism of cardiac glycosides in cancer therapeutics. Expert Opin Investig Drugs 2009;18(2):241-3
91. Riganti C, Doublier S, Viarisio D, et al. Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1alpha and P-glycoprotein overexpression. Br J Pharmacol 2009;156(7):1054-66
92. Rong YP, Bultynck G, Aromolaran AS, et al. The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor. Proc Natl Acad Sci USA 2009;106(34):14397-402
93. 2+-driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IP3 receptor interaction. Blood 2011;10117(10):2924-34
94. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 2009;43:67-93
95. Ravikumar B, Sarkar S, Davies JE, et al. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 2010;90(4):1383-435
96. Kung CP, Budina A, Balaburski G, et al. Autophagy in tumor suppression and cancer therapy. Crit Rev Eukaryot Gene Expr 2011;21(1):71-100
97. Qu X, Yu J, Bhagat G, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003;112(12):1809-20
98. Yue Z, Jin S, Yang C, et al. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA 2003;100(25):15077-82
99. Scarlatti F, Granata R, Meijer AJ, et al. Does autophagy have a license to kill mammalian cells? Cell Death Differ 2009;16(1):12-20
100. Decuypere JP, Bultynck G, Parys JB. A dual role for Ca(2+) in autophagy regulation. Cell Calcium 2011;50(3):242-50
101. Cardenas C, Foskett JK. Mitochondrial Ca(2+) signals in autophagy. Cell Calcium 2012;52(1):44-51
102. Høyer-Hansen M, Bastholm L, Szyniarowski P, et al. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2. Mol Cell 2007;2625(2):193-205
103. Ahmad A, Sakr WA, Rahman KM. Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. Curr Drug Targets 2010;11(6):652-66
104. Clinical trials database search results. Available from: http://clinicaltrials.gov/ct2/results?term=diindolylmethane [Last accessed 12 July 2012]
105. Kandala PK, Srivastava SK. Regulation of macroautophagy in ovarian cancer cells in vitro and in vivo by controlling Glucose regulatory protein 78 and AMPK. Oncotarget 2012;3(4):435-49
106. Law BY, Wang M, Ma DL, et al. Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis. Mol Cancer Ther 2010;9(3):718-30
107. Hsin IL, Ou CC, Wu TC, et al. GMI, an immunomodulatory protein from Ganoderma microsporum, induces autophagy in non-small cell lung cancer cells. Autophagy 2011;7(8):873-82
108. Criollo A, Maiuri MC, Tasdemir E, et al. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ 2007;14(5):1029-39
109. Vicencio JM, Ortiz C, Criollo A, et al. The inositol 1, 4, 5-trisphosphate receptor regulates autophagy through its interaction with Beclin 1. Cell Death Differ 2009;16(7):1006-17
110. Decuypere JP, Welkenhuyzen K, Luyten T, et al. Ins(1, 4, 5) P3 receptor-mediated Ca2+ signaling and autophagy induction are interrelated. Autophagy 2011;7(12):1472-89
111. Cardenas C, Miller RA, Smith I, et al. Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria. Cell 2010;23142(2):270-83
112. Prevarskaya N, Skryma R, Shuba Y. Calcium in tumour metastasis: new roles for known actors. Nat Rev Cancer 2011;2211(8):609-18
113. Su LT, Agapito MA, Li M, et al. TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain. J Biol Chem 2006;21281(16):11260-70
114. Chen JP, Luan Y, You CX, et al. TRPM7 regulates the migration of human nasopharyngeal carcinoma cell by mediating Ca(2+) influx. Cell Calcium 2010;47(5):425-32
115. Wei C, Wang X, Chen M, et al. Calcium flickers steer cell migration. Nature 2009;12457(7231):901-5
116. Wondergem R, Ecay TW, Mahieu F, et al. HGF/SF and menthol increase human glioblastoma cell calcium and migration. Biochem Biophys Res Commun 2008;18372(1):210-15
117. Okamoto Y, Ohkubo T, Ikebe T, et al. Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines. Int J Oncol 2012;40(5):1431-40
118. Waning J, Vriens J, Owsianik G, et al. A novel function of capsaicin-sensitive TRPV1 channels: involvement in cell migration. Cell Calcium 2007;42(1):17-25
119. Monet M, Lehen'kyi V, Gackiere F, et al. Role of cationic channel TRPV2 in promoting prostate cancer migration and progression to androgen resistance. Cancer Res 2010;170(3):1225-35
120. Yang S, Zhang JJ, Huang XY. Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell 2009;315(2):124-34
121. Hammadi M, Chopin V, Matifat F, et al. Human ether a-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry. J Cell Physiol 2012;doi: 10.1002/jcp.24095
122. Huang JB, Kindzelskii AL, Clark AJ, et al. Identification of channels promoting calcium spikes and waves in HT1080 tumor cells: their apparent roles in cell motility and invasion. Cancer Res 2004;164(7):2482-9
123. Kang SS, Han KS, Ku BM, et al. Caffeine-mediated inhibition of calcium release channel inositol 1, 4, 5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival. Cancer Res 2010;170(3):1173-83
124. Mueller A, Bachi T, Hochli M, et al. Subcellular distribution of S100 proteins in tumor cells and their relocation in response to calcium activation. Histochem Cell Biol 1999;111(6):453-9
125. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002;29(6 Suppl 16):15-18
126. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005;69(Suppl 3):4-10
127. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008;8(8):579-91
128. Munaron L. Intracellular calcium, endothelial cells and angiogenesis. Recent Pat Anticancer Drug Discov 2006;1(1):105-19
129. Fiorio Pla A, Avanzato D, Munaron L, et al. Ion channels and transporters in cancer. 6. Vascularizing the tumor: TRP channels as molecular targets. Am J Physiol Cell Physiol 2012;302(1):C9-15
130. Faehling M, Kroll J, Fohr KJ, et al. Essential role of calcium in vascular endothelial growth factor A-induced signaling: mechanism of the antiangiogenic effect of carboxyamidotriazole. FASEB J 2002;16(13):1805-7
131. Clinical Trials database search results. Available from: http://clinicaltrials.gov/ct2/results?term=carboxyamidotriazole [Last accessed 12 July 2012]
132. Enfissi A, Prigent S, Colosetti P, et al. The blocking of capacitative calcium entry by 2-aminoethyl diphenylborate (2-APB) and carboxyamidotriazole (CAI) inhibits proliferation in Hep G2 and Huh-7 human hepatoma cells. Cell Calcium 2004;36(6):459-67
133. Abdullaev IF, Bisaillon JM, Potier M, et al. Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ Res 2008;21103(11):1289-99
134. Li J, Cubbon RM, Wilson LA, et al. Orai1 and CRAC channel dependence of VEGF-activated Ca2+ entry and endothelial tube formation. Circ Res 2011;13108(10):1190-8
135. Kwan HY, Huang Y, Yao X. TRP channels in endothelial function and dysfunction. Biochim Biophys Acta 2007;1772(8):907-14
136. Cheng HW, James AF, Foster RR, et al. VEGF activates receptor-operated cation channels in human microvascular endothelial cells. Arterioscler Thromb Vasc Biol 2006;26(8):1768-76
137. Ge R, Tai Y, Sun Y, et al. Critical role of TRPC6 channels in VEGF-mediated angiogenesis. Cancer Lett 2009;28283(1):43-51
138. Munaron L, Genova T, Avanzato D, et al. Targeting Calcium Channels to Block Tumor Vascularization. Recent Pat Anticancer Drug Discov 2012;25Epub ahead of print
139. Pande J, Szewczyk MM, Grover AK. Allosteric inhibitors of plasma membrane Ca pumps: invention and applications of caloxins. World J Biol Chem 2011;262(3):39-47
140. Muscella A, Calabriso N, Vetrugno C, et al. The platinum (II) complex [Pt(O, O'-acac)(gamma-acac)(DMS)] alters the intracellular calcium homeostasis in MCF-7 breast cancer cells. Biochem Pharmacol 2011;181(1):91-103
141. Tian F, Schrodl K, Kiefl R, et al. The hedgehog pathway inhibitor GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells. Anticancer Res 2012;32(1):89-94
142. De Smaele E, Ferretti E, Gulino A. Vismodegib, a small-molecule inhibitor of the hedgehog pathway for the treatment of advanced cancers. Curr Opin Investig Drugs 2010;11(6):707-18
143. Clinical Trials database search results. Available from: http://clinicaltrials.gov/ct2/results?term=vismodegib+cancer [Last accessed 12 July 2012]
144. Anderluh G, Macek P. Cytolytic peptide and protein toxins from sea anemones (Anthozoa: actiniaria). Toxicon 2002;40(2):111-24
145. Tilley SJ, Saibil HR. The mechanism of pore formation by bacterial toxins. Curr Opin Struct Biol 2006;16(2):230-6
146. Horimoto M, Sasaki Y, Ugawa S, et al. A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer. Cancer Gene Ther 2000;7(10):1341-7
147. Kay MA. State-of-the-art gene-based therapies: the road ahead. Nat Rev Genet 2011;12(5):316-28
148. Zhao L, Wu J, Zhou H, et al. Local gene delivery for cancer therapy. Curr Gene Ther 2011;11(5):423-32
149. Pardo LA, Stuhmer W. Eag1: an emerging oncological target. Cancer Res 2008;1568(6):1611-13
150. Wissenbach U, Niemeyer B, Himmerkus N, et al. TRPV6 and prostate cancer: cancer growth beyond the prostate correlates with increased TRPV6 Ca2+ channel expression. Biochem Biophys Res Commun 2004;1322(4):1359-63
151. Bidaux G, Flourakis M, Thebault S, et al. Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function. J Clin Invest 2007;117(6):1647-57
152. Duncan LM, Deeds J, Hunter J, et al. Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer Res 1998;158(7):1515-20
153. Marchi S, Rimessi A, Giorgi C, et al. Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2+-dependent apoptotic stimuli. Biochem Biophys Res Commun 2008;31375(4):501-5
154. Szado T, Vanderheyden V, Parys JB, et al. Phosphorylation of inositol 1, 4, 5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis. Proc Natl Acad Sci USA 2008;105(7):2427-32
155. Giorgi C, Ito K, Lin HK, et al. PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 2010;26330(6008):1247-51
156. Rimessi A, Marchi S, Fotino C, et al. Intramitochondrial calcium regulation by the FHIT gene product sensitizes to apoptosis. Proc Natl Acad Sci USA 2009;106(31):12753-8
157. Fedida-Metula S, Feldman B, Koshelev V, et al. Lipid rafts couple store-operated Ca2+ entry to constitutive activation of PKB/Akt in a Ca2+/calmodulin-, Src-and PP2A-mediated pathway and promote melanoma tumor growth. Carcinogenesis 2012;33(4):740-50
158. Clinical Trials database search results. Available from: http://clinicaltrials.gov/ct2/results?term=artemisinin+cancer [Last accessed 12 July 2012]
159. Clinical Trials database search results. Available from: http://clinicaltrials.gov/ct2/results?term=digoxin+cancer [Last accessed 12 July 2012]
160. Clinical Trials database search results. Available from: http://clinicaltrials.gov/ct2/show/NCT00017446? term=CP4071&rank=2 [Last accessed 12 July 2012]