Eag and HERG potassium channels as novel therapeutic targets in cancer

Jemal A: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60 (5): 277-300. 10.3322/caac.20073.

Fiske JL: Voltage-sensitive ion channels and cancer. Cancer Metastasis Rev. 2006, 25 (3): 493-500. 10.1007/s10555-006-9017-z.

Swartz KJ: Sensing voltage across lipid membranes. Nature. 2008, 456 (7224): 891-7. 10.1038/nature07620.

Brayden JE, Nelson MT: Regulation of arterial tone by activation of calcium-dependent potassium channels. Science. 1992, 256 (5056): 532-5. 10.1126/science.1373909.

Darszon A: Ion channels in sperm motility and capacitation. Soc Reprod Fertil Suppl. 2007, 65: 229-44.

Lang F: Mechanisms and significance of cell volume regulation. J Am Coll Nutr. 2007, 26 (5 Suppl): 613S-623S.

Sontheimer H: An unexpected role for ion channels in brain tumor metastasis. Exp Biol Med (Maywood). 2008, 233 (7): 779-91. 10.3181/0711-MR-308.

Blackiston DJ, McLaughlin KA, Levin M: Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle. Cell Cycle. 2009, 8 (21): 3519-28.

Perrin MJ: Human ether-a-go-go related gene (hERG) K+ channels: function and dysfunction. Prog Biophys Mol Biol. 2008, 98 (2-3): 137-48. 10.1016/j.pbiomolbio.2008.10.006.

Pardo LA: Role of voltage-gated potassium channels in cancer. J Membr Biol. 2005, 205 (3): 115-24. 10.1007/s00232-005-0776-1.

Conti M: Targeting K+ channels for cancer therapy. J Exp Ther Oncol. 2004, 4 (2): 161-6.

Catsch A: Eine erbliche storung des Bewegungsmechanismus be Drosophila Melanogaster. Z Ind Abst Vererb. 1944, 82: 62-66.

Kaplan WD, Trout WE: The behavior of four neurological mutants of Drosophila. Genetics. 1969, 61 (2): 399-409.

Ganetzky B, Wu CF: Drosophila mutants with opposing effects on nerve excitability: genetic and spatial interactions in repetitive firing. J Neurophysiol. 1982, 47 (3): 501-14.

Warmke JW, Ganetzky B: A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci USA. 1994, 91 (8): 3438-42. 10.1073/pnas.91.8.3438.

Harmar AJ: IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic Acids Res. 2009, D680-5. 10.1093/nar/gkn728. 37 Database

Ludwig J: Functional expression of a rat homologue of the voltage gated ether a go-go potassium channel reveals differences in selectivity and activation kinetics between the Drosophila channel and its mammalian counterpart. EMBO J. 1994, 13 (19): 4451-8.

Frings S: Characterization of ether-a-go-go channels present in photoreceptors reveals similarity to IKx, a K+ current in rod inner segments. J Gen Physiol. 1998, 111 (4): 583-99. 10.1085/jgp.111.4.583.

Occhiodoro T: Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion. FEBS Lett. 1998, 434 (1-2): 177-82. 10.1016/S0014-5793(98)00973-9.

Bijlenga P: T-type alpha 1 H Ca2+ channels are involved in Ca2+ signaling during terminal differentiation (fusion) of human myoblasts. Proc Natl Acad Sci USA. 2000, 97 (13): 7627-32. 10.1073/pnas.97.13.7627.

Curran ME: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995, 80 (5): 795-803. 10.1016/0092-8674(95)90358-5.

Pardo LA: Oncogenic potential of Eag K channels. EMBO J. 1999, 18 (20): 5540-7. 10.1093/emboj/18.20.5540.

Martin S: Eag1 potassium channel immunohistochemistry in the CNS of adult rat and selected regions of human brain. Neuroscience. 2008, 155 (3): 833-44. 10.1016/j.neuroscience.2008.05.019.

Wu CF: Potassium currents in Drosophila: different components affected by mutations of two genes. Science. 1983, 220 (4601): 1076-8. 10.1126/science.6302847.

Bergquist S, Dickman DK, Davis GW: A hierarchy of cell intrinsic and target-derived homeostatic signaling. Neuron. 2010, 66 (2): 220-34. 10.1016/j.neuron.2010.03.023.

Dubin AE, Liles MM, Harris GL: The K+ channel gene ether a go-go is required for the transduction of a subset of odorants in adult Drosophila melanogaster. J Neurosci. 1998, 18 (15): 5603-13.

Titus SA, Warmke JW, Ganetzky B: The Drosophila erg K+ channel polypeptide is encoded by the seizure locus. J Neurosci. 1997, 17 (3): 875-81.

Bauer CK, Schwarz JR: Physiology of EAG K+ channels. J Membr Biol. 2001, 182 (1): 1-15.

Sanguinetti MC: A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell. 1995, 81 (2): 299-307. 10.1016/0092-8674(95)90340-2.

Brugada R: Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation. 2004, 109 (1): 30-5. 10.1161/01.CIR.0000109482.92774.3A.

Warmke J, Drysdale R, Ganetzky B: A distinct potassium channel polypeptide encoded by the Drosophila eag locus. Science. 1991, 252 (5012): 1560-2. 10.1126/science.1840699.

Yellen G: The voltage-gated potassium channels and their relatives. Nature. 2002, 419 (6902): 35-42. 10.1038/nature00978.

Morais Cabral JH: Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain. Cell. 1998, 95 (5): 649-55. 10.1016/S0092-8674(00)81635-9.

Semenza GL: Hypoxia-inducible factor 1 and the molecular physiology of oxygen homeostasis. J Lab Clin Med. 1998, 131 (3): 207-14. 10.1016/S0022-2143(98)90091-9.

Downie BR: Eag1 expression interferes with hypoxia homeostasis and induces angiogenesis in tumors. J Biol Chem. 2008, 283 (52): 36234-40. 10.1074/jbc.M801830200.

Ludwig J, Owen D, Pongs O: Carboxy-terminal domain mediates assembly of the voltage-gated rat ether-a-go-go potassium channel. EMBO J. 1997, 16 (21): 6337-45. 10.1093/emboj/16.21.6337.

Jenke M: C-terminal domains implicated in the functional surface expression of potassium channels. EMBO J. 2003, 22 (3): 395-403. 10.1093/emboj/cdg035.

Sun XX, Bostrom SL, Griffith LC: Alternative splicing of the eag potassium channel gene in Drosophila generates a novel signal transduction scaffolding protein. Mol Cell Neurosci. 2009, 40 (3): 338-43. 10.1016/j.mcn.2008.11.005.

Ganetzky B: The eag family of K+ channels in Drosophila and mammals. Ann N Y Acad Sci. 1999, 868: 356-69. 10.1111/j.1749-6632.1999.tb11297.x.

Bianchi L: herg encodes a K+ current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells?. Cancer Res. 1998, 58 (4): 815-22.

Toral C: Effect of extracellular matrix on adhesion, viability, actin cytoskeleton and K+ currents of cells expressing human ether a go-go channels. Life Sci. 2007, 81 (3): 255-65. 10.1016/j.lfs.2007.05.014.

Meyer R: Identification of ether a go-go and calcium-activated potassium channels in human melanoma cells. J Membr Biol. 1999, 171 (2): 107-15. 10.1007/s002329900563.

Meyer R, Heinemann SH: Characterization of an eag-like potassium channel in human neuroblastoma cells. J Physiol. 1998, 508 (Pt 1): 49-56.

Patt S: Expression of ether a go-go potassium channels in human gliomas. Neurosci Lett. 2004, 368 (3): 249-53. 10.1016/j.neulet.2004.07.001.

Farias LM: Ether a go-go potassium channels as human cervical cancer markers. Cancer Res. 2004, 64 (19): 6996-7001. 10.1158/0008-5472.CAN-04-1204.

Ousingsawat J: Expression of voltage-gated potassium channels in human and mouse colonic carcinoma. Clin Cancer Res. 2007, 13 (3): 824-31. 10.1158/1078-0432.CCR-06-1940.

Ding XW: Aberrant expression of Eag1 potassium channels in gastric cancer patients and cell lines. Med Oncol. 2007, 24 (3): 345-50. 10.1007/s12032-007-0015-y.

Mello de Queiroz F: Ether a go-go potassium channel expression in soft tissue sarcoma patients. Mol Cancer. 2006, 5: 42-10.1186/1476-4598-5-42.

Arcangeli A: A novel inward-rectifying K+ current with a cell-cycle dependence governs the resting potential of mammalian neuroblastoma cells. J Physiol. 1995, 489 (Pt 2): 455-71.

Hofmann G: HERG K+ channels activation during beta(1) integrin-mediated adhesion to fibronectin induces an up-regulation of alpha(v)beta(3) integrin in the preosteoclastic leukemia cell line FLG 29.1. J Biol Chem. 2001, 276 (7): 4923-31. 10.1074/jbc.M005682200.

Smith GA: Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells. J Biol Chem. 2002, 277 (21): 18528-34. 10.1074/jbc.M200592200.

Crociani O: Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells. J Biol Chem. 2003, 278 (5): 2947-55. 10.1074/jbc.M210789200.

Suzuki T, Takimoto K: Selective expression of HERG and Kv2 channels influences proliferation of uterine cancer cells. Int J Oncol. 2004, 25 (1): 153-9.

Shao XD: The potent inhibitory effects of cisapride, a specific blocker for human ether-a-go-go-related gene (HERG) channel, on gastric cancer cells. Cancer Biol Ther. 2005, 4 (3): 295-301. 10.4161/cbt.4.3.1500.

Masi A: hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines. Br J Cancer. 2005, 93 (7): 781-92. 10.1038/sj.bjc.6602775.

Cherubini A: HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium. Br J Cancer. 2000, 83 (12): 1722-9. 10.1054/bjoc.2000.1497.

Pillozzi S: 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 (9): 1791-8. 10.1038/sj.leu.2402572.

Bauer CK: HERG K(+) currents in human prolactin-secreting adenoma cells. Pflugers Arch. 2003, 445 (5): 589-600.

Lastraioli E: herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells. Cancer Res. 2004, 64 (2): 606-11. 10.1158/0008-5472.CAN-03-2360.

Shao XD: Expression and significance of HERG protein in gastric cancer. Cancer Biol Ther. 2008, 7 (1): 45-50. 10.4161/cbt.7.1.5126.

Afrasiabi E: Expression and significance of HERG (KCNH2) potassium channels in the regulation of MDA-MB-435 S melanoma cell proliferation and migration. Cell Signal. 22 (1): 57-64. 10.1016/j.cellsig.2009.09.010.

Wadhwa S: Differential expression of potassium ion channels in human renal cell carcinoma. Int Urol Nephrol. 2008

Ding XW: Aberrant expression of ether a go-go potassium channel in colorectal cancer patients and cell lines. World J Gastroenterol. 2007, 13 (8): 1257-61.

Agarwal JR: The potassium channel Ether a go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia. Mol Cancer. 2010, 9: 18-10.1186/1476-4598-9-18.

Diaz L: Estrogens and human papilloma virus oncogenes regulate human ether-a-go-go-1 potassium channel expression. Cancer Res. 2009, 69 (8): 3300-7. 10.1158/0008-5472.CAN-08-2036.

Borowiec AS: IGF-1 activates hEAG K(+) channels through an Akt-dependent signaling pathway in breast cancer cells: role in cell proliferation. J Cell Physiol. 2007, 212 (3): 690-701. 10.1002/jcp.21065.

Gavrilova-Ruch O, Schonherr R, Heinemann SH: Activation of hEAG1 potassium channels by arachidonic acid. Pflugers Arch. 2007, 453 (6): 891-903. 10.1007/s00424-006-0173-3.

Stuhmer W: Potassium channels as tumour markers. FEBS Lett. 2006, 580 (12): 2850-2. 10.1016/j.febslet.2006.03.062.

Bruggemann A, Stuhmer W, Pardo LA: Mitosis-promoting factor-mediated suppression of a cloned delayed rectifier potassium channel expressed in Xenopus oocytes. Proc Natl Acad Sci USA. 1997, 94 (2): 537-42. 10.1073/pnas.94.2.537.

Pardo LA: Cell cycle-related changes in the conducting properties of r-eag K+ channels. J Cell Biol. 1998, 143 (3): 767-75. 10.1083/jcb.143.3.767.

Camacho J: Cytoskeletal interactions determine the electrophysiological properties of human EAG potassium channels. Pflugers Arch. 2000, 441 (2-3): 167-74. 10.1007/s004240000420.

Arcangeli A: Expression and role of hERG channels in cancer cells. Novartis Found Symp. 2005, 266: 225-32. full_text. discussion 232-4

Xia Z: The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999, 13 (6): 338-47. 10.1002/(SICI)1099-0461(1999)13:6<338::AID-JBT8>3.0.CO;2-7.

Wang H: HERG K+ channel, a regulator of tumor cell apoptosis and proliferation. Cancer Res. 2002, 62 (17): 4843-8.

Nilius B, Schwarz G, Droogmans G: Control of intracellular calcium by membrane potential in human melanoma cells. Am J Physiol. 1993, 265 (6 Pt 1): C1501-10.

Whitaker M, Patel R: Calcium and cell cycle control. Development. 1990, 108 (4): 525-42.

Rouzaire-Dubois B, Dubois JM: A quantitative analysis of the role of K+ channels in mitogenesis of neuroblastoma cells. Cell Signal. 1991, 3 (4): 333-9. 10.1016/0898-6568(91)90062-Y.

Rouzaire-Dubois B, Dubois JM: K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation. J Physiol. 1998, 510 (Pt 1): 93-102. 10.1111/j.1469-7793.1998.093bz.x.

Abbott NJ: Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat. 2002, 200 (6): 629-38. 10.1046/j.1469-7580.2002.00064.x.

Bender AS: Ionic mechanisms in glutamate-induced astrocyte swelling: role of K+ influx. J Neurosci Res. 1998, 52 (3): 307-21. 10.1002/(SICI)1097-4547(19980501)52:3<307::AID-JNR7>3.0.CO;2-H.

Bertout JA, Patel SA, Simon MC: The impact of O2 availability on human cancer. Nat Rev Cancer. 2008, 8 (12): 967-75. 10.1038/nrc2540.

Hegle AP, Marble DD, Wilson GF: A voltage-driven switch for ion-independent signaling by ether-a-go-go K+ channels. Proc Natl Acad Sci USA. 2006, 103 (8): 2886-91. 10.1073/pnas.0505909103.

Sun XX: The eag potassium channel binds and locally activates calcium/calmodulin-dependent protein kinase II. J Biol Chem. 2004, 279 (11): 10206-14. 10.1074/jbc.M310728200.

Colomer J, Means AR: Physiological roles of the Ca2+/CaM-dependent protein kinase cascade in health and disease. Subcell Biochem. 2007, 45: 169-214. full_text.

Hemmerlein B: Overexpression of Eag1 potassium channels in clinical tumours. Mol Cancer. 2006, 5: 41-10.1186/1476-4598-5-41.

Pardo LA, Stuhmer W: Eag1: an emerging oncological target. Cancer Res. 2008, 68 (6): 1611-3. 10.1158/0008-5472.CAN-07-5710.

Garcia-Ferreiro RE: Mechanism of block of hEag1 K+ channels by imipramine and astemizole. J Gen Physiol. 2004, 124 (4): 301-17. 10.1085/jgp.200409041.

Gavrilova-Ruch O: Effects of imipramine on ion channels and proliferation of IGR1 melanoma cells. J Membr Biol. 2002, 188 (2): 137-49. 10.1007/s00232-001-0181-3.

Gomez-Varela D: Monoclonal antibody blockade of the human Eag1 potassium channel function exerts antitumor activity. Cancer Res. 2007, 67 (15): 7343-9. 10.1158/0008-5472.CAN-07-0107.

Weber C: Silencing the activity and proliferative properties of the human EagI Potassium Channel by RNA Interference. J Biol Chem. 2006, 281 (19): 13030-7. 10.1074/jbc.M600883200.

Zhao J: Silencing of herg gene by shRNA inhibits SH-SY5Y cell growth in vitro and in vivo. Eur J Pharmacol. 2008, 579 (1-3): 50-7. 10.1016/j.ejphar.2007.10.008.

Furlan F: ERG conductance expression modulates the excitability of ventral horn GABAergic interneurons that control rhythmic oscillations in the developing mouse spinal cord. J Neurosci. 2007, 27 (4): 919-28. 10.1523/JNEUROSCI.4035-06.2007.

Overholt JL: HERG-Like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body. J Neurophysiol. 2000, 83 (3): 1150-7.

Farrelly AM: Expression and function of KCNH2 (HERG) in the human jejunum. Am J Physiol Gastrointest Liver Physiol. 2003, 284 (6): G883-95.

Gullo F: ERG K+ channel blockade enhances firing and epinephrine secretion in rat chromaffin cells: the missing link to LQT2-related sudden death?. FASEB J. 2003, 17 (2): 330-2.

Rosati B: Glucose- and arginine-induced insulin secretion by human pancreatic beta-cells: the role of HERG K(+) channels in firing and release. FASEB J. 2000, 14 (15): 2601-10. 10.1096/fj.00-0077com.