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Sigma 1 Receptor and Ion Channel Dynamics in Cancer

  • Olivier SorianiEmail author
  • Raphaël Rapetti-Mauss
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 964)

Abstract

SigmaR1 is a multitasking chaperone protein which has mainly been studied in CNS physiological and pathophysiological processes such as pain, memory, neurodegenerative diseases (amyotrophic lateral sclerosis , Parkinson’s and Alzheimer’s diseases, retinal neurodegeneration), stroke and addiction. Strikingly, G-protein and ion channels are the main client protein fami lies of this atypical chaperone and the recent advances that have been performed for the last 10 years demonstrate that SigmaR1 is principally activated following tissue injury and disease development to promote cell survival. In this chapter, we synthesize the data enhancing our comprehension of the interaction between SigmaR1 and ion channels and the unexpected consequences of such functional coupling in cancer development. We also describe a model in which the pro-survival functions of SigmaR1 observed in CNS pathologies are hijacked by cancer cells to shape their electrical signature and behavior in response to the tumor microenvironment.

Keywords

Sigma1R Ion channels Cancer Cell cycle Tumour microenvironment Extra cellular matrix Integrin Angiogenesis Invasion 

Bibliography

  1. 1.
    Chu UB, Ruoho AE (2016) Biochemical pharmacology of the sigma-1 receptor. Mol Pharmacol 89(1):142–153Google Scholar
  2. 2.
    Su TP, Su TC, Nakamura Y, Tsai SY (2016) The sigma-1 receptor as a pluripotent modulator in living systems. Trends Pharmacol Sci 37(4):262–278Google Scholar
  3. 3.
    Hayashi T, Su TP (2007) Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell 131(3):596–610Google Scholar
  4. 4.
    Crottes D, Guizouarn H, Martin P, Borgese F, Soriani O (2013) The sigma-1 receptor: a regulator of cancer cell electrical plasticity? Front Physiol 4:175Google Scholar
  5. 5.
    Ruscher K et al (2011) The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke. Brain 134(Pt 3):732–746Google Scholar
  6. 6.
    Al-Saif A, Al-Mohanna F, Bohlega S (2011) A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann Neurol 70(6):913–919Google Scholar
  7. 7.
    Mavlyutov TA et al (2013) Lack of sigma-1 receptor exacerbates ALS progression in mice. Neuroscience 240:129–134Google Scholar
  8. 8.
    Lahmy V et al (2013) Blockade of Tau Hyperphosphorylation and Abeta generation by the Aminotetrahydrofuran Derivative ANAVEX2-73, a mixed muscarinic and sigma receptor Agonist, in a Nontransgenic mouse model of Alzheimer’s disease. Neuropsychopharmacology 27(4):562–574Google Scholar
  9. 9.
    Wang J, Saul A, Roon P, Smith SB (2016) Activation of the molecular chaperone, sigma 1 receptor, preserves cone function in a murine model of inherited retinal degeneration. Proc Natl Acad Sci U S A 113(26):E3764–E3772Google Scholar
  10. 10.
    Tsai SY et al (2015) Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope. Proc Natl Acad Sci U S A 112(47):E6562–E6570Google Scholar
  11. 11.
    Crottes D et al (2016) SIGMAR1 regulates membrane electrical activity in response to extracellular matrix stimulation to drive cancer cell invasiveness. Cancer Res 76(3):607–618Google Scholar
  12. 12.
    Renaudo A, L’Hoste S, Guizouarn H, Borgese F, Soriani O (2007) Cancer cell cycle modulated by a functional coupling between sigma-1 receptors and Cl- channels. J Biol Chem 282(4):2259–2267Google Scholar
  13. 13.
    Carnally SM, Johannessen M, Henderson RM, Jackson MB, Edwardson JM (2010) Demonstration of a direct interaction between sigma-1 receptors and acid-sensing ion channels. Biophys J 98(7):1182–1191Google Scholar
  14. 14.
    Wong AY et al (2016) Aberrant subcellular dynamics of Sigma-1 receptor mutants underlying neuromuscular diseases. Mol Pharmacol 90(3):238–253Google Scholar
  15. 15.
    Renaudo A et al (2004) Inhibition of tumor cell proliferation by sigma ligands is associated with K+ Channel inhibition and p27kip1 accumulation. J Pharmacol Exp Ther 311(3):1105–1114Google Scholar
  16. 16.
    Vilner BJ, John CS, Bowen WD (1995) Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines. Cancer Res 55(2):408–413Google Scholar
  17. 17.
    Vilner BJ, Decosta BR, Bowen WD (1995) Cytotoxic effects of sigma ligands: sigma receptor- mediated alterations in cellular morphology and viability. J Neurosci 15:117–134Google Scholar
  18. 18.
    Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5(12):993–996Google Scholar
  19. 19.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: The next generation. Cell 144(5):646–674Google Scholar
  20. 20.
    Prevarskaya N, Skryma R, Shuba Y (2010) Ion channels and the hallmarks of cancer. Trends Mol Med 16(3):107–121Google Scholar
  21. 21.
    Arcangeli A (2011) Ion channels in the tumor cell-microenvironment cross talk. Am J Physiol Cell Physiol 301(4):C762–C771Google Scholar
  22. 22.
    Huang X et al (2012) Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics. Genes Dev 26(16):1780–1796Google Scholar
  23. 23.
    Gueguinou M et al (2014) KCa and Ca(2+) channels: the complex thought. Biochim Biophys Acta 1843(10):2322–2333Google Scholar
  24. 24.
    Brisson L, Reshkin SJ, Gore J, Roger S (2012) pH regulators in invadosomal functioning: proton delivery for matrix tasting. Eur J Cell Biol 91(11–12):847–860Google Scholar
  25. 25.
    Pardo LA, Stuhmer W (2014) The roles of K(+) channels in cancer. Nature reviews. Cancer 14(1):39–48Google Scholar
  26. 26.
    Kourrich S, Su TP, Fujimoto M, Bonci A (2012) The sigma-1 receptor: roles in neuronal plasticity and disease. Trends Neurosci 35(12):762–771Google Scholar
  27. 27.
    Hanner M et al (1996) Purification, molecular cloning, and expression of the mammalian sigma1-binding site. Proc Natl Acad Sci U S A 93(15):8072–8077Google Scholar
  28. 28.
    Sircar R, Nichtenhauser R, Ieni JR, Zukin SR (1986) Characterization and autoradiographic visualization of (+)-[3H]SKF10,047 binding in rat and mouse brain: further evidence for phencyclidine/"sigma opiate" receptor commonality. J Pharmacol Exp Ther 237(2):681–688Google Scholar
  29. 29.
    Sircar R, Zukin SR (1986) Further evidence of phencyclidine/sigma opioid receptor commonality. NIDA Res Monogr 64:14–23Google Scholar
  30. 30.
    Rao TS et al (1990) BMY-14802 antagonizes harmaline- and D-serine-induced increases in mouse cerebellar cyclic GMP: neurochemical evidence for a sigma receptor-mediated functional modulation of responses mediated by the N-methyl-D-aspartate receptor complex in vivo. Mol Pharmacol 37(6):978–982Google Scholar
  31. 31.
    Maurice T, Su TP (2009) The pharmacology of sigma-1 receptors. Pharmacol Ther 124(2):195–206Google Scholar
  32. 32.
    Kennedy C, Henderson G (1990) Inhibition of potassium currents by the sigma receptor ligand (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine in sympathetic neurons of the mouse isolated hypogastric ganglion. Neuroscience 3:725–733Google Scholar
  33. 33.
    Wu XZ, Bell JA, Spivak CE, London ED, Su TP (1991) Electrophysiological and binding studies on intact NCB-20 cells suggest presence of low affinity sigma receptor. J Pharmacol Exp Ther 257:351–359Google Scholar
  34. 34.
    Soriani O et al (1999) The sigma-ligand (+)-pentazocine depresses M current and enhances calcium conductances in frog melanotrophs. Am J Phys 277(1 Pt 1):E73–E80Google Scholar
  35. 35.
    Soriani O et al (1999) A-Current down-modulated by sigma receptor in frog pituitary melanotrope cells through a G protein-dependent pathway. J Pharmacol Exp Ther 289(1):321–328Google Scholar
  36. 36.
    Soriani O, Vaudry H, Mei YA, Roman F, Cazin L (1998) Sigma ligands stimulate the electrical activity of frog pituitary melanotrope cells through a G-protein-dependent inhibition of potassium conductances. J Pharmacol Exp Ther 286(1):163–171Google Scholar
  37. 37.
    Lupardus PJ et al (2000) Membrane-delimited coupling between sigma receptors and K+ channels in rat neurohypophysial terminals requires neither G-protein nor ATP. J Physiol 526(Pt 3):527–539Google Scholar
  38. 38.
    Morin-Surun MP, Collin T, Denavit-Saubie M, Baulieu EE, Monnet FP (1999) Intracellular sigma1 receptor modulates phospholipase C and protein kinase C activities in the brainstem. Proc Natl Acad Sci U S A 96(14):8196–8199Google Scholar
  39. 39.
    He YL et al (2012) Cyproheptadine enhances the I(K) of mouse cortical neurons through sigma-1 receptor-mediated intracellular signal pathway. PLoSOne 7(7):e41303Google Scholar
  40. 40.
    Aydar E, Palmer CP, Klyachko VA, Jackson MB (2002) The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron JID – 8809320 34(3):399–410Google Scholar
  41. 41.
    Crottes D et al (2011) Sig1R protein regulates hERG channel expression through a post-translational mechanism in leukemic cells. J Biol Chem 286(32):27947–27958Google Scholar
  42. 42.
    Wu Z, Bowen WD (2008) Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: constitutive enhancement of calcium signaling in MCF-7 tumor cells. J Biol Chem 283(42):28198–28215Google Scholar
  43. 43.
    Balasuriya D et al (2012) The sigma-1 receptor binds to the Nav1.5 voltage-gated Na+ channel with 4-fold symmetry. J Biol Chem 287(44):37021–37029Google Scholar
  44. 44.
    Sanguinetti MC, Jiang C, Curran ME, Keating MT (1995) A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81(2):299–307Google Scholar
  45. 45.
    Trudeau MC, Warmke JW, Ganetzky B, Robertson GA (1995) HERG, a human inward rectifier in the voltage-gated potassium channel family. Science 269(5220):92–95Google Scholar
  46. 46.
    Vandenberg JI et al (2012) hERG K(+) channels: structure, function, and clinical significance. Physiol Rev 92(3):1393–1478Google Scholar
  47. 47.
    Ficker E, Dennis AT, Wang L, Brown AM (2003) Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG. Circ Res 92(12):e87–100Google Scholar
  48. 48.
    Sharma P et al (2010) Endoplasmic reticulum protein targeting of phospholamban: A common role for an N-terminal di-arginine motif in ER retention? PLoS One 5(7):e11496Google Scholar
  49. 49.
    Duden R (2003) ER-to-Golgi transport: COP I and COP II function (Review). Mol Membr Biol 20(3):197–207Google Scholar
  50. 50.
    Balasuriya D et al (2014) A direct interaction between the sigma-1 receptor and the hERG voltage-gated K+ channel revealed by atomic force microscopy and homogeneous time-resolved fluorescence (HTRF(R)). J Biol Chem 289(46):32353–32363Google Scholar
  51. 51.
    Balasuriya D, Stewart AP, Edwardson JM (2013) The sigma-1 receptor interacts directly with GluN1 but not GluN2A in the GluN1/GluN2A NMDA receptor. J Neuro sci 33(46):18219–18224Google Scholar
  52. 52.
    Kourrich S et al (2013) Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine. Cell 152(1–2):236–247Google Scholar
  53. 53.
    Pabba M et al (2014) NMDA receptors are upregulated and trafficked to the plasma membrane after sigma-1 receptor activation in the rat hippocampus. J Neurosci 34(34):11325–11338Google Scholar
  54. 54.
    Hogan PG, Rao A (2007) Dissecting ICRAC, a store-operated calcium current. Trends Biochem Sci 32(5):235–245Google Scholar
  55. 55.
    Srivats S et al (2016) Sigma1 receptors inhibit store-operated Ca2+ entry by attenuating coupling of STIM1 to Orai1. J Cell Biol 213(1):65–79Google Scholar
  56. 56.
    Mavlyutov TA et al (2016) Sigma-1 receptor expression in the dorsal root ganglion: Reexamination using a highly specific antibody. Neuroscience 331:148–157Google Scholar
  57. 57.
    Mavlyutov TA, Epstein M, Guo LW (2015) Subcellular localization of the sigma-1 receptor in retinal neurons – an electron microscopy study. Sci Report 5:10689Google Scholar
  58. 58.
    Tsai SY, Hayashi T, Mori T, Su TP (2009) Sigma-1 receptor chaperones and diseases. Cent Nerv Syst Agents Med Chem 9(3):184–189Google Scholar
  59. 59.
    Chantome A et al (2013) Pivotal role of the lipid Raft SK3-Orai1 complex in human cancer cell migration and bone metastases. Cancer Res 73(15):4852–4861Google Scholar
  60. 60.
    Brisson L et al (2011) Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae. Oncogene 30(17):2070–2076Google Scholar
  61. 61.
    Nelson M, Millican-Slater R, Forrest LC, Brackenbury WJ (2014) The sodium channel beta1 subunit mediates outgrowth of neurite-like processes on breast cancer cells and promotes tumour growth and metastasis. Int J Cancer 135(10):2338–2351Google Scholar
  62. 62.
    Warnier M et al (2015) CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and angiogenesis. Oncogene 34(42):5383–5394Google Scholar
  63. 63.
    Pedersen SF, Hoffmann EK, Novak I (2013) Cell volume regulation in epithelial physiology and cancer. Front Physiol 4:233Google Scholar
  64. 64.
    Hoffmann EK (2011) Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells. Cell Physiol Biochem 28(6):1061–1078Google Scholar
  65. 65.
    Rouzaire-Dubois B, Milandri JB, Bostel S, Dubois JM (2000) Control of cell proliferation by cell volume alterations in rat C6 glioma cells. Pflugers Arch 440(6):881–888Google Scholar
  66. 66.
    Rouzaire-Dubois B, Bostel S, Dubois JM (1999) Evidence for several mechanisms of volume regulation in neuroblastoma x glioma hybrid NG108-15 cells. Neuroscience 88(1):307–317Google Scholar
  67. 67.
    Sherr CJ, Roberts JM (1995) Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev JID – 8711660 9(10):1149–1163Google Scholar
  68. 68.
    Zerfass-Thome K et al (1997) p27KIP1 blocks cyclin E-dependent transactivation of cyclin A gene expression. Mol Cell Biol JID – 8109087 17(1):407–415CrossRefGoogle Scholar
  69. 69.
    Maeno E, Ishizaki Y, Kanaseki T, Hazama A, Okada Y (2000) Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci U S A 97(17):9487–9492Google Scholar
  70. 70.
    Bortner CD, Scoltock AB, Sifre MI, Cidlowski JA (2012) Osmotic stress resistance imparts acquired anti-apoptotic mechanisms in lymphocytes. J Biol Chem 287(9):6284–6295Google Scholar
  71. 71.
    Ciesielski J, Su TP, Tsai SY (2016) Myristic acid hitchhiking on sigma-1 receptor to fend off neurodegeneration. Receptors Clin Investig 3(1): pii: e1114Google Scholar
  72. 72.
    Mavlyutov TA, Guo LW, Epstein ML, Ruoho AE (2015) Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS). J Pharmacol Sci 127(1):10–16Google Scholar
  73. 73.
    Reshkin SJ, Cardone RA, Harguindey S (2012) Na+−H+ exchanger, pH regulation and cancer. Recent Pat Anticancer Drug Discov 8(1):85–95Google Scholar
  74. 74.
    Li L, Hanahan D (2013) Hijacking the neuronal NMDAR signaling circuit to promote tumor growth and invasion. Cell 153(1):86–100Google Scholar
  75. 75.
    Crociani O et al (2013) hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer. Sci Rep 3:3308Google Scholar
  76. 76.
    Masi A et al (2005) hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines. Br J Cancer 93(7):781–792Google Scholar
  77. 77.
    Pillozzi S et al (2011) Chemotherapy resistance in acute lymphoblastic leukemia requires hERG1 channels and is overcome by hERG1 blockers. Blood 117(3):902–914Google Scholar
  78. 78.
    Pillozzi S et al (2007) VEGFR-1 (FLT-1), beta1 integrin, and hERG K+ channel for a macromolecular signaling complex in acute myeloid leukemia: Role in cell migration and clinical outcome. Blood 110(4):1238–1250CrossRefPubMedGoogle Scholar
  79. 79.
    Arcangeli A, Becchetti A (2010) Integrin structure and functional relation with ion channels. Adv Exp Med Biol 674:1–7Google Scholar
  80. 80.
    Lastraioli E et al (2004) herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells. Cancer Res 64(2):606–611Google Scholar
  81. 81.
    Beacham DA, Amatangelo MD, Cukierman E (2007) Preparation of extracellular matrices produced by cultured and primary fibroblasts. Curr Protoc Cell Biol. Chapter 10:UnitGoogle Scholar
  82. 82.
    Goetz JG et al (2011) Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 146(1):148–163CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    bou-Lovergne A et al (2011) Investigation of the role of sigma1-receptors in inositol 1,4,5-trisphosphate dependent calcium signaling in hepatocytes. Cell Calcium 50(1):62–72CrossRefGoogle Scholar
  84. 84.
    Kinoshita M, Matsuoka Y, Suzuki T, Mirrielees J, Yang J (2012) Sigma-1 receptor alters the kinetics of Kv1.3 voltage gated potassium channels but not the sensitivity to receptor ligands. Brain Res 1452:1–9Google Scholar
  85. 85.
    Ruscher K, Wieloch T (2015) The involvement of the sigma-1 receptor in neurodegeneration and neurorestoration. J Pharmacol Sci 127(1):30–35Google Scholar
  86. 86.
    Chantome A, et al (2011) Ion channels as promising therapeutic targets for melanoma. In: Yohei T (ed) Breakthroughs in melanoma research (Intech), pp 429–460Google Scholar
  87. 87.
    Fontanilla D et al (2009) The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator. Science 323(5916):934–937Google Scholar
  88. 88.
    Zhang H, Katnik C, Cuevas J (2009) Sigma receptor activation inhibits voltage-gated sodium channels in rat intracardiac ganglion neurons. Intern J Physiol Pathophysiol Pharmacol 2(1):1–11Google Scholar
  89. 89.
    Tchedre KT et al (2008) Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction. Invest Ophthalmol Vis Sci 49(11):4993–5002Google Scholar
  90. 90.
    Herrera Y et al (2008) sigma-1 receptor modulation of acid-sensing ion channel a (ASIC1a) and ASIC1a-induced Ca2+ influx in rat cortical neurons. J Pharmacol Exp Ther 327(2):491–502Google Scholar
  91. 91.
    Hayashi T, Su TP (2001) Regulating ankyrin dynamics: Roles of sigma-1 receptors. Proc Natl Acad Sci U S A 98(2):491–496Google Scholar
  92. 92.
    Prause J et al (2013) Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis. Hum Mol Genet 22(8):1581–1600Google Scholar

Copyright information

© Springer International Publishing AG (outside the USA) 2017

Authors and Affiliations

  1. 1.University of Nice Sophia Antipolis, CNRS, Inserm, iBVNiceFrance
  2. 2.Bâtiment Sciences Naturelles; UFR SciencesNiceFrance

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