Voltage-gated ion channels in cancer cell proliferation

Cancers

Volumn 7, Issue 2, 2015, Pages 849-875

  Rao, Vidhya R ^a   Perez Neut, Mathew ^a   Kaja, Simon ^b   Gentile, Saverio ^a  

^a LOYOLA UNIVERSITY CHICAGO   (United States)

^b UNIVERSITY OF MISSOURI KANSAS CITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer; Cell proliferation; Membrane potential; Voltage gated ion channel

Indexed keywords

BUFALIN; CATION CHANNEL; ION TRANSPORT AFFECTING AGENT; NS 1643; POTASSIUM CHANNEL HERG; POTASSIUM CHANNEL KV1.3; POTASSIUM CHANNEL KV1.5; UNCLASSIFIED DRUG; VOLTAGE GATED CALCIUM CHANNEL; VOLTAGE GATED CALCIUM CHANNEL 1; VOLTAGE GATED CALCIUM CHANNEL 3; VOLTAGE GATED CALCIUM CHANNEL ALPHA 2 DELTA SUBUNIT; VOLTAGE GATED CHLORIDE CHANNEL; VOLTAGE GATED POTASSIUM CHANNEL; VOLTAGE GATED SODIUM CHANNEL;

ANTINEOPLASTIC ACTIVITY; CANCER CELL; CANCER GROWTH; CANCER THERAPY; CELL PROLIFERATION; HUMAN; MEMBRANE POTENTIAL; METASTASIS; MOLECULARLY TARGETED THERAPY; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION;

EID: 84930935379     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers7020813     Document Type: Review

References (171)

1. Stewart, B., Wild, C. World Cancer Report; IARC Press: Lyon, France, 2014.
2. Cone, C.D., Jr.; Tongier, M., Jr. Mitotic synchronization of L-strain fibroblasts with 5-aminouracil as determined by time-lapse cinephotography. NASA TN D-5021. Tech. Note U.S. Natl. Aeronaut. Space Adm. 1969. [PubMed]
3. DeSantis, C.E.; Lin, C.C.; Mariotto, A.B.; Siegel, R.L.; Stein, K.D.; Kramer, J.L.; Alteri, R.; Robbins, A.S.; Jemal, A. Cancer treatment and survivorship statistics, 2014. CA Cancer J. Clin. 2014, 64, 252–271. [CrossRef] [PubMed]
4. Weinberg, R. The Biology of Cancer; Garland Science: New York, NY, USA, 2007.
5. Pecorino, L. Molecular Biology of Cancer: Mechanisms, Targets, and Therapeutics; Oxford University Press: Oxford, UK, 2012.
6. Hanahan, D., Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. [CrossRef] [PubMed]
7. Ouyang, L.; Shi, Z.; Zhao, S.; Wang, F.T.; Zhou, T.T.; Liu, B.; Bao, J.K. Programmed Cell Death Pathways in Cancer: A Review of Apoptosis, Autophagy and Programmed Necrosis. Cell Prolif. 2012, 45, 487–498. [CrossRef] [PubMed]
8. Li, M.; Xiong, Z.-G. Ion Channels as Targets for Cancer Therapy. Int. J. Physiol. Pathophysiol. Pharmacol. 2011, 3, 156. [PubMed]
9. Pedersen, S.F.; Stock, C. Ion channels and transporters in cancer: Pathophysiology, regulation, and clinical potential. Cancer Res. 2013, 73, 1658–1661. [CrossRef] [PubMed]
10. Djamgoz, M.B.; Coombes, R.C.; Schwab, A. Ion transport and cancer: From initiation to metastasis. Philos. Trans. R Soc. Lond. B Biol. Sci. 2014, 369, 20130092. [CrossRef] [PubMed]
11. Golias, C.H.; Charalabopoulos, A.; Charalabopoulos, K. Cell proliferation and cell cycle control: A mini review. Int. J. Clin. Pract. 2004, 58, 1134–1141. [CrossRef] [PubMed]
12. Vermeulen, K.; van Bockstaele, D.R.; Berneman, Z.N. The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell. Prolif. 2003, 36, 131–149. [CrossRef] [PubMed]
13. Yang, M.; Brackenbury, W.J. Membrane potential and cancer progression. Front. Physiol. 2013, 4, 185. [CrossRef] [PubMed]
14. Blackiston, D.J.; McLaughlin, K.A.; Levin, M. Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle. Cell Cycle 2009, 8, 3527–3536. [CrossRef] [PubMed]
15. Wright, S.H. Generation of resting membrane potential. Adv. Physiol. Educ. 2004, 28, 139–142. [CrossRef] [PubMed]
16. Cone, C.D., Jr. Electroosmotic interactions accompanying mitosis initation in sarcoma cells in vitro. Trans. NY Acad. Sci. 1969, 31, 404–427. [CrossRef]
17. Cone, C.D., Jr.; Tongier, M., Jr. Control of somatic cell mitosis by simulated changes in the transmembrane potential level. Oncology 1971, 25, 168–182. [CrossRef] [PubMed]
18. Stillwell, E.F.; Cone, C.M.; Cone, C.D., Jr. Stimulation of DNA synthesis in CNS neurones by sustained depolarisation. Nat. New Biol. 1973, 246, 110–111. [CrossRef] [PubMed]
19. Wonderlin, W.F.; Woodfork, K.A.; Strobl, J.S. Changes in membrane potential during the progression of MCF-7 human mammary tumor cells through the cell cycle. J. Cell. Physiol. 1995, 165, 177–185. [CrossRef] [PubMed]
20. Boonstra, J.; Mummery, C.L.; Tertoolen, L.G.; van der Saag, P.T.; de Laat, S.W. Cation transport and growth regulation in neuroblastoma cells. Modulations of K+ transport and electrical membrane properties during the cell cycle. J. Cell. Physiol. 1981, 107, 75–83. [CrossRef] [PubMed]
21. Cone, C.D., Jr.; Cone, C.M. Induction of mitosis in mature neurons in central nervous system by sustained depolarization. Science 1976, 192, 155–158. [CrossRef] [PubMed]
22. Sachs, H.G.; Stambrook, P.J.; Ebert, J.D. Changes in membrane potential during the cell cycle. Exp. Cell. Res. 1974, 83, 362–366. [CrossRef] [PubMed]
23. Sundelacruz, S.; Levin, M.; Kaplan, D.L. Role of membrane potential in the regulation of cell proliferation and differentiation. Stem Cell Rev. 2009, 5, 231–246. [CrossRef] [PubMed]
24. Huang, X.; Jan, L.Y. Targeting potassium channels in cancer. J. Cell Biol. 2014, 206, 151–162. [CrossRef] [PubMed]
25. Bezanilla, F. Voltage-gated ion channels. IEEE Trans. Nanobioscience 2005, 4, 34–48.
26. Catterall, W.A. Structure and function of voltage-gated ion channels. Annu. Rev. Biochem. 1995, 64, 493–531. [CrossRef] [PubMed]
27. Armstrong, C.M.; Hille, B. Voltage-gated ion channels and electrical excitability. Neuron 1998, 20, 371–380. [CrossRef] [PubMed]
28. Miller, C. An overview of the potassium channel family. Genome Biol. 2000, 1, 1–5. [CrossRef] [PubMed]
29. Pardo, L.A.; del Camino, D.; Sanchez, A.; Alves, F.; Bruggemann, A.; Beckh, S.; Stuhmer, W. Oncogenic potential of EAG K(+) channels. EMBO J. 1999, 18, 5540–5547. [CrossRef] [PubMed]
30. Hemmerlein, B.; Weseloh, R.M.; Mello de Queiroz, F.; Knotgen, H.; Sanchez, A.; Rubio, M.E.; Martin, S.; Schliephacke, T.; Jenke, M.; Heinz Joachim, R., et al. Overexpression of Eag1 potassium channels in clinical tumours. Mol. Cancer 2006, 5, 41. [CrossRef] [PubMed]
31. Patt, S.; Preussat, K.; Beetz, C.; Kraft, R.; Schrey, M.; Kalff, R.; Schonherr, K.; Heinemann, S.H. Expression of ether a go-go potassium channels in human gliomas. Neurosci. Lett. 2004, 368, 249–253. [CrossRef] [PubMed]
32. Mello de Queiroz, F.; Suarez-Kurtz, G.; Stuhmer, W.; Pardo, L.A. Ether a go-go potassium channel expression in soft tissue sarcoma patients. Mol. Cancer 2006, 5, 42. [CrossRef] [PubMed]
33. Ding, X.W.; Luo, H.S.; Jin, X.; Yan, J.J., Ai, Y.W. Aberrant expression of Eag1 potassium channels in gastric cancer patients and cell lines. Med. Oncol. 2007, 24, 345–350. [CrossRef] [PubMed]
34. Ding, X.W.; Yan, J.J.; An, P.; Lu, P.; Luo, H.S. Aberrant expression of ether a go-go potassium channel in colorectal cancer patients and cell lines. World J. Gastroenterol. 2007, 13, 1257–1261. [CrossRef] [PubMed]
35. Ousingsawat, J.; Spitzner, M.; Puntheeranurak, S.; Terracciano, L.; Tornillo, L.; Bubendorf, L.; Kunzelmann, K.; Schreiber, R. Expression of voltage-gated potassium channels in human and mouse colonic carcinoma. Clin. Cancer Res. 2007, 13, 824–831. [CrossRef] [PubMed]
36. Gomez-Varela, D.; Zwick-Wallasch, E.; Knotgen, H.; Sanchez, A.; Hettmann, T.; Ossipov, D.; Weseloh, R.; Contreras-Jurado, C.; Rothe, M.; Stuhmer, W., et al. Monoclonal antibody blockade of the human Eag1 potassium channel function exerts antitumor activity. Cancer Res. 2007, 67, 7343–7349. [CrossRef] [PubMed]
37. Hartung, F.; Stuhmer, W.; Pardo, L.A. Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via bifunctional TRAIL antibody. Mol. Cancer 2011, 10, 109. [CrossRef] [PubMed]
38. Asher, V.; Sowter, H.; Shaw, R.; Bali, A.; Khan, R. Eag and HERG potassium channels as novel therapeutic targets in cancer. World J. Surg. Oncol. 2010, 8, 113. [CrossRef] [PubMed]
39. Weber, C.; Mello de Queiroz, F.; Downie, B.R.; Suckow, A.; Stuhmer, W.; Pardo, L.A. Silencing the activity and proliferative properties of the human EagI Potassium Channel by RNA Interference. J. Biol. Chem. 2006, 281, 13030–13037. [CrossRef] [PubMed]
40. Warmke, J.W.; Ganetzky, B. A family of potassium channel genes related to eag in Drosophila and mammals. Proc. Natl. Acad. Sci. USA 1994, 91, 3438–3442. [CrossRef] [PubMed]
41. Vandenberg, J.I.; Perry, M.D.; Perrin, M.J.; Mann, S.A.; Ke, Y., Hill, A.P. hERG K(+) channels: structure, function, and clinical significance. Physiol. Rev. 2012, 92, 1393–1478. [CrossRef] [PubMed]
42. Babcock, J.J.; Li, M. hERG channel function: Beyond long QT. Acta Pharmacol. Sin. 2013, 34, 329–335. [CrossRef] [PubMed]
43. Arcangeli, A. Expression and role of hERG channels in cancer cells. Novartis Found. Symp. 2005, 266, 225–234.
44. Wang, H.; Zhang, Y.; Cao, L.; Han, H.; Wang, J.; Yang, B.; Nattel, S.; Wang, Z. HERG K+ channel, a regulator of tumor cell apoptosis and proliferation. Cancer Res. 2002, 62, 4843–4848. [PubMed]
45. Glassmeier, G.; Hempel, K.; Wulfsen, I.; Bauer, C.K.; Schumacher, U.; Schwarz, J.R. Inhibition of HERG1 K+ channel protein expression decreases cell proliferation of human small cell lung cancer cells. Pflugers. Arch. 2012, 463, 365–376. [CrossRef] [PubMed]
46. Staudacher, I.; Jehle, J.; Staudacher, K.; Pledl, H.W.; Lemke, D.; Schweizer, P.A.; Becker, R.; Katus, H.A.; Thomas, D. HERG K+ channel-dependent apoptosis and cell cycle arrest in human glioblastoma cells. PLoS ONE 2014, 9, e88164. [CrossRef] [PubMed]
47. Jehle, J.; Schweizer, P.A.; Katus, H.A.; Thomas, D. Novel roles for hERG K(+) channels in cell proliferation and apoptosis. Cell Death Dis. 2011, 2, e193. [CrossRef] [PubMed]
48. Perez-Neut, M.; Shum, A.; Cuevas, B.D.; Miller, R.; Gentile, S. Stimulation of hERG1 channel activity promotes a calcium-dependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells. Oncotarget 2015, 6, 1631–1639. [PubMed]
49. Lee, Y.S.; Sayeed, M.M., Wurster, R.D. Inhibition of cell growth by K+ channel modulators is due to interference with agonist-induced Ca2+ release. Cell. Signal. 1993, 5, 803–809. [CrossRef] [PubMed]
50. Hegle, A.P.; Marble, D.D.; Wilson, G.F. A voltage-driven switch for ion-independent signaling by ether-a-go-go K+ channels. Proc. Natl. Acad. Sci. USA 2006, 103, 2886–2891. [CrossRef] [PubMed]
51. Downie, B.R.; Sanchez, A.; Knotgen, H.; Contreras-Jurado, C.; Gymnopoulos, M.; Weber, C.; Stuhmer, W.; Pardo, L.A. Eag1 expression interferes with hypoxia homeostasis and induces angiogenesis in tumors. J. Biol. Chem. 2008, 283, 36234–36240. [CrossRef] [PubMed]
52. Cidad, P.; Jimenez-Perez, L.; Garcia-Arribas, D.; Miguel-Velado, E.; Tajada, S.; Ruiz-McDavitt, C.; Lopez-Lopez, J.R.; Perez-Garcia, M.T. Kv1.3 channels can modulate cell proliferation during phenotypic switch by an ion-flux independent mechanism. Arterioscler. Thromb. Vasc. Biol. 2012, 32, 1299–1307. [CrossRef] [PubMed]
53. Wonderlin, W.F.; Strobl, J.S. Potassium channels, proliferation and G1 progression. J. Membr. Biol. 1996, 154, 91–107. [CrossRef] [PubMed]
54. Woodfork, K.A.; Wonderlin, W.F.; Peterson, V.A.; Strobl, J.S. Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle arrest of human breast cancer cells in tissue culture. J. Cell. Physiol. 1995, 162, 163–171. [CrossRef] [PubMed]
55. Wang, W.; Fan, Y.; Wang, S.; Wang, L.; He, W.; Zhang, Q.; Li, X. Effects of voltage-gated K+ channel on cell proliferation in multiple myeloma. Sci. World J. 2014. [CrossRef]
56. Nilius, B.; Schwarz, G.; Droogmans, G. Control of intracellular calcium by membrane potential in human melanoma cells. Am. J. Physiol. 1993, 265, C1501–C1510. [PubMed]
57. Gelfand, E.W.; Cheung, R.K.; Grinstein, S. Role of membrane potential in the regulation of lectin-induced calcium uptake. J. Cell. Physiol. 1984, 121, 533–539. [CrossRef] [PubMed]
58. Lepple-Wienhues, A.; Berweck, S.; Bohmig, M.; Leo, C.P.; Meyling, B.; Garbe, C.; Wiederholt, M. K+ channels and the intracellular calcium signal in human melanoma cell proliferation. J. Membr. Biol. 1996, 151, 149–157. [CrossRef] [PubMed]
59. Menendez, S.T.; Villaronga, M.A.; Rodrigo, J.P.; Alvarez-Teijeiro, S.; Garcia-Carracedo, D.; Urdinguio, R.G.; Fraga, M.F.; Pardo, L.A.; Viloria, C.G.; Suarez, C., et al. Frequent aberrant expression of the human ether a go-go (hEAG1) potassium channel in head and neck cancer: Pathobiological mechanisms and clinical implications. J. Mol. Med. (Berl.) 2012, 90, 1173–1184. [CrossRef]
60. Ouadid-Ahidouch, H.; Rodat-Despoix, L.; Matifat, F.; Morin, G.; Ahidouch, A. DNA methylation of channel-related genes in cancers. Biochim. Biophys. Acta 2015. [CrossRef]
61. Feng, Q.; Hawes, S.E.; Stern, J.E.; Wiens, L.; Lu, H.; Dong, Z.M.; Jordan, C.D.; Kiviat, N.B., Vesselle, H. DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients. Cancer Epidemiol. Biomarkers Prev. 2008, 17, 645–654. [CrossRef] [PubMed]
62. Cicek, M.S.; Koestler, D.C.; Fridley, B.L.; Kalli, K.R.; Armasu, S.M.; Larson, M.C.; Wang, C.; Winham, S.J.; Vierkant, R.A., Rider, D.N., et al. Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel. Hum. Mol. Genet. 2013, 22, 3038–3047. [CrossRef] [PubMed]
63. Lin, H.; Li, Z.; Chen, C.; Luo, X.; Xiao, J.; Dong, D.; Lu, Y.; Yang, B.; Wang, Z. Transcriptional and post-transcriptional mechanisms for oncogenic overexpression of ether a go-go K+ channel. PLoS ONE 2011, 6, e20362. [CrossRef] [PubMed]
64. Martin, N.P.; Marron Fernandez de Velasco, E., Mizuno, F.; Scappini, E.L.; Gloss, B.; Erxleben, C.; Williams, J.G.; Stapleton, H.M.; Gentile, S.; Armstrong, D.L. A rapid cytoplasmic mechanism for PI3 kinase regulation by the nuclear thyroid hormone receptor, TRbeta, and genetic evidence for its role in the maturation of mouse hippocampal synapses in vivo. Endocrinology 2014, 155, 3713–3724. [CrossRef] [PubMed]
65. Gentile, S.; Darden, T.; Erxleben, C.; Romeo, C.; Russo, A.; Martin, N.; Rossie, S.; Armstrong, D.L. Rac GTPase signaling through the PP5 protein phosphatase. Proc. Natl. Acad. Sci. USA 2006, 103, 5202–5206. [CrossRef] [PubMed]
66. Storey, N.M.; Gentile, S.; Ullah, H.; Russo, A.; Muessel, M.; Erxleben, C.; Armstrong, D.L. Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone. Proc. Natl. Acad. Sci. USA 2006, 103, 5197–5201. [CrossRef] [PubMed]
67. Simoncini, T.; Genazzani, A.R. Non-genomic actions of sex steroid hormones. Eur. J. Endocrinol. 2003, 148, 281–292. [CrossRef] [PubMed]
68. Furukawa, T.; Kurokawa, J. Non-genomic regulation of cardiac ion channels by sex hormones. Cardiovasc. Hematol. Disord. Drug Targets 2008, 8, 245–251. [CrossRef] [PubMed]
69. Arcangeli, A.; Yuan, J.X. American Journal of Physiology-Cell Physiology theme: Ion channels and transporters in cancer. Am. J. Physiol. Cell Physiol. 2011, 301, C253–C254. [CrossRef]
70. Ouadid-Ahidouch, H.; Roudbaraki, M.; Delcourt, P.; Ahidouch, A.; Joury, N.; Prevarskaya, N. Functional and molecular identification of intermediate-conductance Ca2+-activated K+ channels in breast cancer cells: Association with cell cycle progression. Am. J. Physiol. Cell Physiol. 2004, 287, C125–C134. [CrossRef] [PubMed]
71. Arcangeli, A.; Bianchi, L.; Becchetti, A.; Faravelli, L.; Coronnello, M.; Mini, E.; Olivotto, M.; Wanke, E. A novel inward-rectifying K+ current with a cell-cycle dependence governs the resting potential of mammalian neuroblastoma cells. J. Physiol. 1995, 489, 455–471. [CrossRef] [PubMed]
72. Villalonga, N.; Martinez-Marmol, R.; Roura-Ferrer, M.; David, M.; Valenzuela, C.; Soler, C.; Felipe, A. Cell cycle-dependent expression of Kv1.5 is involved in myoblast proliferation. Biochim. Biophys. Acta 2008, 1783, 728–736. [CrossRef]
73. Huang, X.; Dubuc, A.M.; Hashizume, R.; Berg, J.; He, Y.; Wang, J.; Chiang, C.; Cooper, M.K.; Northcott, P.A.; Taylor, M.D., et al. Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics. Genes Dev. 2012, 26, 1780–1796. [CrossRef] [PubMed]
74. MacLean, J.N.; Zhang, Y.; Johnson, B.R.; Harris-Warrick, R.M. Activity-independent homeostasis in rhythmically active neurons. Neuron 2003, 37, 109–120. [CrossRef] [PubMed]
75. Holmes, T.C.; Berman, K.; Swartz, J.E.; Dagan, D.; Levitan, I.B. Expression of voltage-gated potassium channels decreases cellular protein tyrosine phosphorylation. J. Neurosci. 1997, 17, 8964–8974. [PubMed]
76. Felipe, A.; Bielanska, J.; Comes, N.; Vallejo, A.; Roig, S.; Ramon, Y.C.S.; Condom, E.; Hernandez-Losa, J.; Ferreres, J.C. Targeting the voltage-dependent K+ channels Kv1.3 and Kv1.5 as tumor biomarkers for cancer detection and prevention. Curr. Med. Chem. 2012, 19, 661–674. [CrossRef] [PubMed]
77. Szabo, I.; Bock, J.; Jekle, A.; Soddemann, M.; Adams, C.; Lang, F.; Zoratti, M.; Gulbins, E. A novel potassium channel in lymphocyte mitochondria. J. Biol. Chem. 2005, 280, 12790–12798. [CrossRef] [PubMed]
78. Szabo, I.; Bock, J.; Grassme, H.; Soddemann, M.; Wilker, B.; Lang, F.; Zoratti, M.; Gulbins, E. Mitochondrial potassium channel Kv1.3 mediates Bax-induced apoptosis in lymphocytes. Proc. Natl Acad. Sci. USA 2008, 105, 14861–14866. [CrossRef] [PubMed]
79. Leanza, L.; Henry, B.; Sassi, N.; Zoratti, M.; Chandy, K.G.; Gulbins, E.; Szabo, I. Inhibitors of mitochondrial Kv1.3 channels induce Bax/Bak-independent death of cancer cells. EMBO Mol. Med. 2012, 4, 577–593. [CrossRef] [PubMed]
80. Bonnet, S.; Archer, S.L.; Allalunis-Turner, J.; Haromy, A.; Beaulieu, C.; Thompson, R.; Lee, C.T.; Lopaschuk, G.D.; Puttagunta, L.; Harry, G., et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 2007, 11, 37–51. [CrossRef] [PubMed]
81. Ransom, C.B.; Liu, X.; Sontheimer, H. Current transients associated with BK channels in human glioma cells. J. Membr. Biol. 2003, 193, 201–213. [CrossRef] [PubMed]
82. Ransom, C.B.; Liu, X.; Sontheimer, H. BK channels in human glioma cells have enhanced calcium sensitivity. Glia 2002, 38, 281–291. [CrossRef] [PubMed]
83. Liu, X.; Chang, Y.; Reinhart, P.H.; Sontheimer, H. Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells. J. Neurosci. 2002, 22, 1840–1849. [PubMed]
84. Simms, B.A.; Zamponi, G.W. Neuronal voltage-gated calcium channels: structure, function, and dysfunction. Neuron 2014, 82, 24–45. [CrossRef] [PubMed]
85. Berridge, M.J. Neuronal calcium signaling. Neuron 1998, 21, 13–26. [CrossRef]
86. Guéguinou, M.; Chantôme, A.; Fromont, G.; Bougnoux, P.; Vandier, C.; Potier-Cartereau, M. KCa and Ca2+ channels: The complex thought. Biochim. Biophys. Acta 2014, 1843, 2322–2333. [CrossRef] [PubMed]
87. Scholl, U.I.; Goh, G.; Stolting, G.; de Oliveira, R.C.; Choi, M.; Overton, J.D.; Fonseca, A.L.; Korah, R.; Starker, L.F.; Kunstman, J.W., et al. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat. Genet. 2013, 45, 1050–1054. [CrossRef] [PubMed]
88. Chen, R.; Zeng, X.; Zhang, R.; Huang, J.; Kuang, X.; Yang, J.; Liu, J.; Tawfik, O.; Thrasher, J.B.; Li, B. Cav1.3 channel alpha1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers. Urol. Oncol. 2014, 32, 524–536. [CrossRef] [PubMed]
89. Kashiwagi, E.; Shiota, M.; Yokomizo, A.; Inokuchi, J.; Uchiumi, T.; Naito, S. EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer. Prostate Cancer Prostatic Dis. 2014, 17, 10–17. [CrossRef] [PubMed]
90. Zhang, Y.; Tao, J.; Huang, H.; Ding, G.; Cheng, Y.; Sun, W. Effects of celecoxib on voltage-gated calcium channel currents in rat pheochromocytoma (PC12) cells. Pharmacol. Res. 2007, 56, 267–274. [CrossRef] [PubMed]
91. Guo, D.Q.; Zhang, H.; Tan, S.J.; Gu, Y.C. Nifedipine promotes the proliferation and migration of breast cancer cells. PLoS ONE 2014, 9, e113649. [CrossRef] [PubMed]
92. Gray, L.S.; Perez-Reyes, E.; Gomora, J.C.; Haverstick, D.M.; Shattock, M.; McLatchie, L.; Harper, J.; Brooks, G.; Heady, T.; Macdonald, T.L. The role of voltage gated T-type Ca2+ channel isoforms in mediating “capacitative” Ca2+ entry in cancer cells. Cell Calcium 2004, 36, 489–497. [CrossRef] [PubMed]
93. Ohkubo, T.; Yamazaki, J. T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells. Int. J. Oncol. 2012, 41, 267–725. [PubMed]
94. Yu, W.; Wang, P.; Ma, H.; Zhang, G.; Yulin, Z.; Lu, B.; Wang, H.; Dong, M. Suppression of T-type Ca2+ channels inhibited human laryngeal squamous cell carcinoma cell proliferation running title: roles of T-type Ca2+ channels in LSCC cell proliferation. Clin. Lab. 2014, 60, 621–628. [PubMed]
95. Das, A.; Pushparaj, C.; Bahi, N.; Sorolla, A.; Herreros, J.; Pamplona, R.; Vilella, R.; Matias-Guiu, X.; Marti, R.M.; Canti, C. Functional expression of voltage-gated calcium channels in human melanoma. Pigment. Cell. Melanoma Res. 2012, 25, 200–212. [CrossRef] [PubMed]
96. Das, A.; Pushparaj, C.; Herreros, J.; Nager, M.; Vilella, R.; Portero, M.; Pamplona, R.; Matias-Guiu, X.; Marti, R.M.; Canti, C. T-type calcium channel blockers inhibit autophagy and promote apoptosis of malignant melanoma cells. Pigment. Cell. Melanoma Res. 2013, 26, 874–885. [CrossRef] [PubMed]
97. Valerie, N.C.; Dziegielewska, B.; Hosing, A.S.; Augustin, E.; Gray, L.S.; Brautigan, D.L.; Larner, J.M.; Dziegielewski, J. Inhibition of T-type calcium channels disrupts Akt signaling and promotes apoptosis in glioblastoma cells. Biochem. Pharmacol. 2013, 85, 888–897. [CrossRef] [PubMed]
98. Zhang, Y.; Zhang, J.; Jiang, D.; Zhang, D.; Qian, Z.; Liu, C.; Tao, J. Inhibition of T-type Ca2+ channels by endostatin attenuates human glioblastoma cell proliferation and migration. Br. J. Pharmacol. 2012, 166, 1247–1260. [CrossRef] [PubMed]
99. Weaver, E.M.; Zamora, F.J.; Puplampu-Dove, Y.A.; Kiessu, E.; Hearne, J.L.; Martin-Caraballo, M. Regulation of T-type calcium channel expression by sodium butyrate in prostate cancer cells. Eur. J. Pharmacol. 2015, 749, 20–31. [CrossRef] [PubMed]
100. Catterall, W.A.; Perez-Reyes, E.; Snutch, T.P.; Striessnig, J. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol. Rev. 2005, 57, 411–425. [CrossRef] [PubMed]
101. Killary, A.M.; Wolf, M.E.; Giambernardi, T.A.; Naylor, S.L. Definition of a tumor suppressor locus within human chromosome 3p21-p22. Proc. Natl. Acad. Sci. USA 1992, 89, 10877–10881. [CrossRef] [PubMed]
102. Gao, B.; Sekido, Y.; Maximov, A.; Saad, M.; Forgacs, E.; Latif, F.; Wei, M.H.; Lerman, M.; Lee, J.H.; Perez-Reyes, E., et al. Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2). J. Biol. Chem. 2000, 275, 12237–12242. [CrossRef] [PubMed]
103. Angeloni, D.; Duh, F.M.; Wei, M.F.; Johnson, B.E.; Lerman, M.I. A G-to-A single nucleotide polymorphism in intron 2 of the human CACNA2D2 gene that maps at 3p21.3. Mol. Cell. Probes 2001, 15, 125–127. [CrossRef] [PubMed]
104. Lerman, M.I.; Minna, J.D. The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: Identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res. 2000, 60, 6116–6133. [PubMed]
105. Carboni, G.L.; Gao, B.; Nishizaki, M.; Xu, K.; Minna, J.D.; Roth, J.A.; Ji, L. CACNA2D2-mediated apoptosis in NSCLC cells is associated with alterations of the intracellular calcium signaling and disruption of mitochondria membrane integrity. Oncogene 2003, 22, 615–626. [CrossRef] [PubMed]
106. Warnier, M.; Roudbaraki, M.; Derouiche, S.; Delcourt, P.; Bokhobza, A.; Prevarskaya, N.; Mariot, P. CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and angiogenesis. Oncogene 2015. [CrossRef]
107. Wanajo, A.; Sasaki, A.; Nagasaki, H.; Shimada, S.; Otsubo, T.; Owaki, S.; Shimizu, Y.; Eishi, Y.; Kojima, K.; Nakajima, Y., et al. Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer. Gastroenterology 2008, 135, 580–590. [CrossRef]
108. Palmieri, C.; Rudraraju, B.; Monteverde, M.; Lattanzio, L.; Gojis, O.; Brizio, R.; Garrone, O.; Merlano, M.; Syed, N.; Lo Nigro, C., et al. Methylation of the calcium channel regulatory subunit alpha2delta-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas. Br. J. Cancer 2012, 107, 375–381. [CrossRef] [PubMed]
109. Wong, A.M.; Kong, K.L.; Chen, L.; Liu, M.; Wong, A.M.; Zhu, C.; Tsang, J.W., Guan, X.Y. Characterization of CACNA2D3 as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma. Int. J. Cancer 2013, 133, 2284–2295. [CrossRef] [PubMed]
110. Li, Y.; Zhu, C.L.; Nie, C.J.; Li, J.C.; Zeng, T.T.; Zhou, J.; Chen, J.; Chen, K.; Fu, L.; Liu, H., et al. Investigation of tumor suppressing function of CACNA2D3 in esophageal squamous cell carcinoma. PLoS ONE 2013, 8, e60027. [CrossRef] [PubMed]
111. Gackiere, F.; Warnier, M.; Katsogiannou, M.; Derouiche, S.; Delcourt, P.; Dewailly, E.; Slomianny, C.; Humez, S.; Prevarskaya, N.; Roudbaraki, M., et al. Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth. Biol. Open 2013, 2, 941–951. [CrossRef] [PubMed]
112. Yu, F.H.; Catterall, W.A. Overview of the voltage-gated sodium channel family. Genome Biol. 2003, 4, 207. [CrossRef] [PubMed]
113. Roger, S.; Rollin, J.; Barascu, A.; Besson, P.; Raynal, P.I.; Iochmann, S.; Lei, M.; Bougnoux, P.; Gruel, Y.; Le Guennec, J.Y. Voltage-gated sodium channels potentiate the invasive capacities of human non-small-cell lung cancer cell lines. Int. J. Biochem. Cell. Biol. 2007, 39, 774–786. [CrossRef] [PubMed]
114. Roger, S.; Potier, M.; Vandier, C.; Besson, P.; Le Guennec, J.Y. Voltage-gated sodium channels: new targets in cancer therapy? Curr. Pharm Des. 2006, 12, 3681–3695. [CrossRef] [PubMed]
115. Fraser, S.P.; Diss, J.K.; Chioni, A.M.; Mycielska, M.E.; Pan, H.; Yamaci, R.F.; Pani, F.; Siwy, Z.; Krasowska, M.; Grzywna, Z., et al. Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin. Cancer Res. 2005, 11, 5381–5389. [CrossRef] [PubMed]
116. Brackenbury, W.J.; Chioni, A.M.; Diss, J.K.; Djamgoz, M.B. The neonatal splice variant of Nav1.5 potentiates in vitro invasive behaviour of MDA-MB-231 human breast cancer cells. Breast Cancer Res. Treat. 2007, 101, 149–160. [CrossRef] [PubMed]
117. Roger, S.; Besson, P.; Le Guennec, J.Y. Involvement of a novel fast inward sodium current in the invasion capacity of a breast cancer cell line. Biochim. Biophys. Acta 2003, 1616, 107–111. [CrossRef] [PubMed]
118. Bennett, E.S.; Smith, B.A.; Harper, J.M. Voltage-gated Na+ channels confer invasive properties on human prostate cancer cells. Pflugers. Arch. 2004, 447, 908–914. [CrossRef] [PubMed]
119. Diss, J.K.; Archer, S.N.; Hirano, J.; Fraser, S.P.; Djamgoz, M.B. Expression profiles of voltage-gated Na(+) channel alpha-subunit genes in rat and human prostate cancer cell lines. Prostate 2001, 48, 165–178. [CrossRef] [PubMed]
120. Diss, J.K.; Stewart, D.; Pani, F.; Foster, C.S.; Walker, M.M.; Patel, A.; Djamgoz, M.B. A potential novel marker for human prostate cancer: Voltage-gated sodium channel expression in vivo. Prostate Cancer Prostatic Dis. 2005, 8, 266–273. [CrossRef]
121. Anderson, J.D.; Hansen, T.P.; Lenkowski, P.W.; Walls, A.M.; Choudhury, I.M.; Schenck, H.A.; Friehling, M.; Holl, G.M.; Patel, M.K.; Sikes, R.A., et al. Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3. Mol. Cancer Ther. 2003, 2, 1149–1154. [PubMed]
122. Nakajima, T.; Kubota, N.; Tsutsumi, T.; Oguri, A.; Imuta, H.; Jo, T.; Oonuma, H.; Soma, M.; Meguro, K.; Takano, H., et al. Eicosapentaenoic acid inhibits voltage-gated sodium channels and invasiveness in prostate cancer cells. Br. J. Pharmacol. 2009, 156, 420–431. [CrossRef] [PubMed]
123. Andrikopoulos, P.; Fraser, S.P.; Patterson, L.; Ahmad, Z.; Burcu, H.; Ottaviani, D.; Diss, J.K.; Box, C.; Eccles, S.A.; Djamgoz, M.B. Angiogenic functions of voltage-gated Na+ Channels in human endothelial cells: Modulation of vascular endothelial growth factor (VEGF) signaling. J. Biol. Chem. 2011, 286, 16846–16860. [CrossRef]
124. Davis, G.C.; Kong, Y.; Paige, M.; Li, Z.; Merrick, E.C.; Hansen, T.; Suy, S.; Wang, K.; Dakshanamurthy, S.; Cordova, A., et al. Asymmetric synthesis and evaluation of a hydroxyphenylamide voltage-gated sodium channel blocker in human prostate cancer xenografts. Bioorg. Med. Chem. 2012, 20, 2180–2188. [CrossRef] [PubMed]
125. Mindell, J.A.; Maduke, M. ClC chloride channels. Genome Biol. 2001, 2, 3000–3001. [CrossRef]
126. Olsen, M.L.; Schade, S.; Lyons, S.A.; Amaral, M.D.; Sontheimer, H. Expression of voltage-gated chloride channels in human glioma cells. J. Neurosci. 2003, 23, 5572–5582. [PubMed]
127. Hong, S.; Bi, M.; Wang, L.; Kang, Z.; Ling, L.; Zhao, C. CLC-3 channels in cancer (review). Oncol. Rep. 2015, 33, 507–514. [PubMed]
128. Habela, C.W.; Ernest, N.J.; Swindall, A.F.; Sontheimer, H. Chloride accumulation drives volume dynamics underlying cell proliferation and migration. J. Neurophysiol. 2009, 101, 750–757. [CrossRef] [PubMed]
129. Habela, C.W.; Sontheimer, H. Cytoplasmic volume condensation is an integral part of mitosis. Cell Cycle 2007, 6, 1613–1620. [CrossRef] [PubMed]
130. Xu, B.; Mao, J.; Wang, L.; Zhu, L.; Li, H.; Wang, W.; Jin, X.; Zhu, J.; Chen, L. ClC-3 chloride channels are essential for cell proliferation and cell cycle progression in nasopharyngeal carcinoma cells. Acta Biochim. Biophys. Sin. (Shanghai) 2010, 42, 370–380. [CrossRef]
131. Li, M.; Wang, B.; Lin, W. Cl-channel blockers inhibit cell proliferation and arrest the cell cycle of human ovarian cancer cells. Eur. J. Gynaecol. Oncol. 2008, 29, 267–271. [PubMed]
132. Li, M.; Wu, D.B.; Wang, J. Effects of volume-activated chloride channels on the invasion and migration of human endometrial cancer cells. Eur. J. Gynaecol. Oncol. 2012, 34, 60–64.
133. Garcia-Ferreiro, R.E.; Kerschensteiner, D.; Major, F.; Monje, F.; Stuhmer, W.; Pardo, L.A. Mechanism of block of hEag1 K+ channels by imipramine and astemizole. J. Gen. Physiol. 2004, 124, 301–317. [CrossRef] [PubMed]
134. Spitzner, M.; Ousingsawat, J.; Scheidt, K.; Kunzelmann, K.; Schreiber, R. Voltage-gated K+ channels support proliferation of colonic carcinoma cells. FASEB J. 2007, 21, 35–44. [CrossRef] [PubMed]
135. Asher, V.; Warren, A.; Shaw, R.; Sowter, H.; Bali, A.; Khan, R. The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line. Cancer Cell. Int. 2011, 11, 6. [CrossRef] [PubMed]
136. Wu, X.; Zhong, D.; Lin, B.; Zhai, W.; Ding, Z.; Wu, J. p38 MAPK regulates the expression of ether a go-go potassium channel in human osteosarcoma cells. Radiol. Oncol. 2013, 47, 42–49. [CrossRef] [PubMed]
137. Jahchan, N.S.; Dudley, J.T.; Mazur, P.K.; Flores, N.; Yang, D.; Palmerton, A.; Zmoos, A.F.; Vaka, D.; Tran, K.Q.; Zhou, M., et al. A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer and other neuroendocrine tumors. Cancer Discov. 2013, 3, 1364–1377. [CrossRef] [PubMed]
138. Gavrilova-Ruch, O.; Schonherr, K.; Gessner, G.; Schonherr, R.; Klapperstuck, T.; Wohlrab, W.; Heinemann, S.H. Effects of imipramine on ion channels and proliferation of IGR1 melanoma cells. J. Membr. Biol. 2002, 188, 137–149. [CrossRef] [PubMed]
139. Ouadid-Ahidouch, H.; Le Bourhis, X.; Roudbaraki, M.; Toillon, R.A.; Delcourt, P.; Prevarskaya, N. Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether.a-gogo K+ channel. Receptors Channels 2001, 7, 345–356. [PubMed]
140. Garcia-Quiroz, J.; Garcia-Becerra, R.; Santos-Martinez, N.; Barrera, D.; Ordaz-Rosado, D.; Avila, E.; Halhali, A.; Villanueva, O.; Ibarra-Sanchez, M.J.; Esparza-Lopez, J., et al. In vivo dual targeting of the oncogenic Ether-a-go-go-1 potassium channel by calcitriol and astemizole results in enhanced antineoplastic effects in breast tumors. BMC Cancer 2014, 14, 745. [CrossRef] [PubMed]
141. Garcia-Quiroz, J.; Camacho, J. Astemizole: An old anti-histamine as a new promising anti-cancer drug. Anticancer Agents Med. Chem. 2011, 11, 307–14. [CrossRef] [PubMed]
142. Pillozzi, S.; Brizzi, M.F.; Balzi, M.; Crociani, O.; Cherubini, A.; Guasti, L.; Bartolozzi, B.; Becchetti, A.; Wanke, E.; Bernabei, P.A., et al. HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors. Leukemia 2002, 16, 1791–1798. [CrossRef] [PubMed]
143. Fiore, A.; Carraresi, L.; Morabito, A.; Polvani, S.; Fortunato, A.; Lastraioli, E.; Femia, A.P.; De Lorenzo, E.; Caderni, G.; Arcangeli, A. Characterization of hERG1 channel role in mouse colorectal carcinogenesis. Cancer Med. 2013, 2, 583–594. [PubMed]
144. Kallergis, E.M.; Goudis, C.A.; Simantirakis, E.N.; Kochiadakis, G.E.; Vardas, P.E. Mechanisms, risk factors, and management of acquired long QT syndrome: A comprehensive review. Sci. World J. 2012. [CrossRef]
145. Ganapathi, S.B.; Kester, M.; Elmslie, K.S. State-dependent block of HERG potassium channels by R-roscovitine: Implications for cancer therapy. Am. J. Physiol. Cell. Physiol. 2009, 296, C701–C710. [CrossRef] [PubMed]
146. Nair, B.C.; Vallabhaneni, S.; Tekmal, R.R.; Vadlamudi, R.K. Roscovitine confers tumor suppressive effect on therapy-resistant breast tumor cells. Breast Cancer Res. 2011, 13, R80. [CrossRef] [PubMed]
147. Benson, C.; White, J.; de Bono, J.; O’Donnell, A.; Raynaud, F.; Cruickshank, C.; McGrath, H.; Walton, M.; Workman, P.; Kaye, S., et al. A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days. Br. J. Cancer 2007, 96, 29–37. [CrossRef] [PubMed]
148. Chouabe, C.; Drici, M.D.; Romey, G.; Barhanin, J.; Lazdunski, M. HERG and KvLQT1/IsK, the cardiac K+ channels involved in long QT syndromes, are targets for calcium channel blockers. Mol. Pharmacol. 1998, 54, 695–703. [PubMed]
149. Millward, M.J.; Cantwell, B.M.; Munro, N.C.; Robinson, A.; Corris, P.A.; Harris, A.L. Oral verapamil with chemotherapy for advanced non-small cell lung cancer: A randomised study. Br. J. Cancer 1993, 67, 1031–1035. [CrossRef] [PubMed]
150. Mouhat, S.; Andreotti, N.; Jouirou, B.; Sabatier, J.M. Animal toxins acting on voltage-gated potassium channels. Curr. Pharm Des. 2008, 14, 2503–2518. [CrossRef] [PubMed]
151. Diochot, S.; Loret, E.; Bruhn, T.; Beress, L.; Lazdunski, M. APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks voltage-gated human ether-a-go-go-related gene potassium channels. Mol. Pharmacol. 2003, 64, 59–69. [CrossRef] [PubMed]
152. Restano-Cassulini, R.; Korolkova, Y.V.; Diochot, S.; Gurrola, G.; Guasti, L.; Possani, L.D.; Lazdunski, M.; Grishin, E.V.; Arcangeli, A.; Wanke, E. Species diversity and peptide toxins blocking selectivity of ether-a-go-go-related gene subfamily K+ channels in the central nervous system. Mol. Pharmacol. 2006, 69, 1673–1683. [CrossRef] [PubMed]
153. Beeton, C.; Pennington, M.W.; Norton, R.S. Analogs of the sea anemone potassium channel blocker ShK for the treatment of autoimmune diseases. Inflamm. Allergy Drug Targets 2011, 10, 313–321. [CrossRef] [PubMed]
154. Yang, M.; Kozminski, D.J.; Wold, L.A.; Modak, R.; Calhoun, J.D.; Isom, L.L.; Brackenbury, W.J. Therapeutic potential for phenytoin: targeting Na(v)1.5 sodium channels to reduce migration and invasion in metastatic breast cancer. Breast Cancer Res. Treat. 2012, 134, 603–615. [CrossRef]
155. Abdul, M.; Hoosein, N. Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells. Anticancer Res. 2001, 21, 2045–2048.
156. Nelson, M.; Yang, M.; Dowle, A.A.; Thomas, J.R.; Brackenbury, W.J. The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis. Mol. Cancer 2015, 14, 13. [CrossRef] [PubMed]
157. Fraser, S.P.; Ozerlat-Gunduz, I.; Brackenbury, W.J.; Fitzgerald, E.M.; Campbell, T.M.; Coombes, R.C.; Djamgoz, M.B. Philos. Regulation of voltage-gated sodium channel expression in cancer: Hormones, growth factors and auto-regulation. Trans. R Soc. Lond. B Biol. Sci. 2014, 369. [CrossRef]
158. Sikes, R.A.; Walls, A.M.; Brennen, W.N.; Anderson, J.D.; Choudhury-Mukherjee, I.; Schenck, H.A.; Brown, M.L. Therapeutic approaches targeting prostate cancer progression using novel voltage-gated ion channel blockers. Clin. Prostate Cancer 2003, 2, 181–187. [CrossRef] [PubMed]
159. Zhang, J.J.; Jacob, T.J.; Valverde, M.A.; Hardy, S.P.; Mintenig, G.M.; Sepulveda, F.V.; Gill, D.R.; Hyde, S.C.; Trezise, A.E.; Higgins, C.F. Tamoxifen blocks chloride channels. A possible mechanism for cataract formation. J. Clin. Invest. 1994, 94, 1690–1697. [CrossRef] [PubMed]
160. Cheng, Y.; Zhao, J.; Qiao, W.; Chen, K. Recent advances in diagnosis and treatment of gliomas using chlorotoxin-based bioconjugates. Am. J. Nucl. Med. Mol. Imaging 2014, 4, 385–405. [PubMed]
161. Deshane, J.; Garner, C.C.; Sontheimer, H. Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2. J. Biol. Chem. 2003, 278, 4135–4144. [CrossRef] [PubMed]
162. The MICAD Research Team. Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. In 131I-Chlorotoxin; National Center for Biotechnology Information (U.S.): Bethesda, MD, USA; 17; July; 2007.
163. Dardevet, L.; Rani, D.; Aziz, T.A.; Bazin, I.; Sabatier, J.M.; Fadl, M.; Brambilla, E.; deWaard, M. Chlorotoxin: A helpful natural scorpion peptide to diagnose glioma and fight tumor invasion. Toxins (Basel) 2015, 7, 1079–1101. [CrossRef]
164. Zhao, J.; Wei, X.L.; Jia, Y.S.; Zheng, J.Q. Silencing of herg gene by shRNA inhibits SH-SY5Y cell growth in vitro and in vivo. Eur. J. Pharmacol. 2008, 579, 50–57. [CrossRef] [PubMed]
165. Sontheimer, H. An unexpected role for ion channels in brain tumor metastasis. Exp. Biol. Med. (Maywood) 2008, 233, 779–791. [CrossRef]
166. Zhu, L.; Yang, H.; Zuo, W.; Yang, L.; Zhang, H.; Ye, W.; Mao, J.; Chen, L.; Wang, L. Differential expression and roles of volume-activated chloride channels in control of growth of normal and cancerous nasopharyngeal epithelial cells. Biochem. Pharmacol. 2012, 83, 324–334. [CrossRef] [PubMed]
167. Chittajallu, R.; Chen, Y.; Wang, H.; Yuan, X.; Ghiani, C.A.; Heckman, T.; McBain, C.J.; Gallo, V. Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle. Proc. Natl. Acad. Sci. USA 2002, 99, 2350–2355. [CrossRef] [PubMed]
168. Habela, C.W.; Olsen, M.L.; Sontheimer, H. ClC3 is a critical regulator of the cell cycle in normal and malignant glial cells. J. Neurosci. 2008, 28, 9205–9217. [CrossRef] [PubMed]
169. Lansu, K.; Gentile, S. Potassium channel activation inhibits proliferation of breast cancer cells by activating a senescence program. Cell. Death Dis. 2013, 4, e652. [CrossRef] [PubMed]
170. Perez-Neut, M.; Rao, V.R.; Gentile, S. hERG1/Kv11.1 activation stimulates transcription of p21waf/cip in breast cancer cells via a calcineurin-dependent mechanism. Oncotarget. 2015. in press.
171. Liu, J.; Zhang, D.; Li, Y.; Chen, W.; Ruan, Z.; Deng, L.; Wang, L.; Tian, H.; Yiu, A.; Fan, C. Discovery of bufadienolides as a novel class of ClC-3 chloride channel activators with antitumor activities. J. Med. Chem. 2013, 56, 5734–5743. [CrossRef] [PubMed]