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Voltage-sensitive ion channels and cancer

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Abstract

Plasma membrane voltage-sensitive ion channels classically have been associated with a variety of inherited diseases or “channelopathies” that range in the severity of symptoms from mild to lethal. Ion channels are found throughout the body and are responsible for facilitated diffusion of ions down the electrochemical gradient across cells membranes in various tissues. Voltage-sensitive ion channels open in response to changes in the membrane potential and are primarily found in excitable cells and tissues. Potassium, calcium, and sodium channels play critical roles in the development of major diseases, such as hyperkalemia, epilepsy, congenital myotonia and several cardiac arrythmias. Recently, cancer studies have begun to define the role of voltage-sensitive ion channels in the progression of cancer to a more malignant phenotype. In cancer, the increased expression or increased kinetics of voltage-sensitive ion channels is associated with an increasing malignant potential as evinced by their role in cell proliferation, migration and survival; as such, these channels are becoming the targets of significant drug development efforts to block or reduce voltage-sensitive ion channel activity in order to prevent or combat malignant disease.

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References

  1. Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Smigal, C., et al. (2006). Cancer statistics, 2006. CA: A Cancer Journal for Clinicians, 56(2), 106–130, Mar–Apr.

    Article  Google Scholar 

  2. Anderson, J. D., Hansen, T. P., Lenkowski, P. W., Walls, A. M., Choudhury, I. M., Schenck, H. A., et al. (2003). Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3. Molecular Cancer Therapeutics, 2(11), 1149–1154, Nov.

    CAS  PubMed  Google Scholar 

  3. Laniado, M. E., Fraser, S. P., & Djamgoz, M. B. (2001). Voltage-gated K(+) channel activity in human prostate cancer cell lines of markedly different metastatic potential: Distinguishing characteristics of PC-3 and LNCaP cells. Prostate, 46(4), 262–274, Mar 1.

    Article  CAS  PubMed  Google Scholar 

  4. Preussat, K., Beetz, C., Schrey, M., Kraft, R., Wolfl, S., Kalff, R., et al. (2003). Expression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas. Neurosci Letters, 346(1–2), 33–36, Jul 31.

    Article  CAS  Google Scholar 

  5. Wang, X. T., Nagaba, Y., Cross, H. S., Wrba, F., Zhang, L., & Guggino, S. E. (2000). The mRNA of L-type calcium channel elevated in colon cancer: Protein distribution in normal and cancerous colon. American Journal of Pathology, 157(5), 1549–1562, Nov.

    CAS  PubMed  Google Scholar 

  6. Sikes, R. A., Walls, A. M., Brennen, W. N., Anderson, J. D., Choudhury-Mukherjee, I., Schenck, H. A., et al. (2003). Therapeutic approaches targeting prostate cancer progression using novel voltage-gated ion channel blockers. Clinical Prostate Cancer, 2(3), 181–187, Dec.

    CAS  PubMed  Google Scholar 

  7. Lehmann-Horn, F., & Jurkat-Rott, K. (1999). Voltage-gated ion channels and hereditary disease. Physiological Reviews, 79(4), 1317–1372, Oct.

    CAS  PubMed  Google Scholar 

  8. Vijayaragavan, K., Powell, A. J., Kinghorn, I. J., & Chahine, M. (2004). Role of auxiliary beta1-, beta2-, and beta3-subunits and their interaction with Na(v)1.8 voltage-gated sodium channel. Biochemical and Biophysical Research Communications, 319(2), 531–540, Jun 25.

    Article  CAS  PubMed  Google Scholar 

  9. Fraser, S. P., Grimes, J. A., & Djamgoz, M. B. (2000). Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: Comparison of strongly and weakly metastatic cell lines. Prostate, 44(1), 61–76, Jun 15.

    Article  CAS  PubMed  Google Scholar 

  10. Grimes, J. A., Fraser, S. P., Stephens, G. J., Downing, J. E., Laniado, M. E., Foster, C. S., et al. (1995). Differential expression of voltage-activated Na+ currents in two prostatic tumour cell lines: contribution to invasiveness in vitro. FEBS Letters, 369(2–3), 290–294, Aug 7.

    Article  CAS  PubMed  Google Scholar 

  11. Skryma, R. N., Prevarskaya, N. B., Dufy-Barbe, L., Odessa, M. F., Audin, J., & Dufy, B. (1997). Potassium conductance in the androgen-sensitive prostate cancer cell line, LNCaP: Involvement in cell proliferation. Prostate, 33(2), 112–122, Oct 1.

    Article  CAS  PubMed  Google Scholar 

  12. Abdul, M., & Hoosein, N. (2002). Voltage-gated potassium ion channels in colon cancer. Oncology Reports, 9(5), 961–964, Sep–Oct.

    CAS  PubMed  Google Scholar 

  13. Chang K. W., Yuan, T. C., Fang, K. P., Yang, F. S., Liu, C. J., Chang, C. S., et al. (2003). The increase of voltage-gated potassium channel Kv3.4 mRNA expression in oral squamous cell carcinoma. Journal of Oral Pathology & Medicine, 32(10), 606–611, Nov.

    Article  CAS  Google Scholar 

  14. Zhou, Z. H., Unlap, T., Li, L., & Ma, H. P. (2002). Incomplete inactivation of voltage-dependent K+ channels in human B lymphoma cells. Journal of Membrane Biology, 188(2), 97–105, Jul 15.

    Article  CAS  PubMed  Google Scholar 

  15. Zhou, Q., Kwan, H. Y., Chan, H. C., Jiang, J. L., Tam, S. C., & Yao, X. (2003). Blockage of voltage-gated K+ channels inhibits adhesion and proliferation of hepatocarcinoma cells. International Journal of Molecular Medicine, 11(2), 261–266, Feb.

    CAS  PubMed  Google Scholar 

  16. Toral, J., Hu, W., Yi, L., Barrett, J. E., Sokol, P. T., & Ziai, M. R. (1994). Use of cultured human neuroblastoma cells in rapid discovery of the voltage-gated potassium-channel blockers. Journal of Pharmacy and Pharmacology, 46(9), 731–734, Sep.

    CAS  PubMed  Google Scholar 

  17. Diss, J. K., Stewart, D., Fraser, S. P., Black, J. A., Dib-Hajj, S., Waxman, S. G., et al. (1998). Expression of skeletal muscle-type voltage-gated Na+ channel in rat and human prostate cancer cell lines. FEBS Letters, 427(1), 5–10, May 1.

    Article  CAS  PubMed  Google Scholar 

  18. Smith, P., Rhodes, N. P., Shortland, A. P., Fraser, S. P., Djamgoz, M. B., Ke, Y., et al. (1998). Sodium channel protein expression enhances the invasiveness of rat and human prostate cancer cells. FEBS Letters, 423(1), 19–24, Feb 13.

    Article  CAS  PubMed  Google Scholar 

  19. Chang, C. C., Acharfi, S., Wu, M. H., Chiang, F. T., Wang, J. K., Sung, T. C., et al. (2004). A novel SCN5A mutation manifests as a malignant form of long QT syndrome with perinatal onset of tachycardia/bradycardia. Cardiovascular Research, 64(2), 268–278, Nov 1.

    Article  CAS  PubMed  Google Scholar 

  20. Gu, X. Q., & Waxman, S. G. (1996). Action potential-like responses in B104 cells with low Na+ channel densities. Brain Research, 735(1), 50–58, Sep 30.

    CAS  PubMed  Google Scholar 

  21. Shih, C., Padhy, L. C., Murray, M., & Weinberg, R. A. (1981). Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature, 290(5803), 261–264, Mar 19.

    Article  CAS  PubMed  Google Scholar 

  22. Schubert, D., Heinemann, S., Carlisle, W., Tarikas, H., Kimes, B., Patrick, J., et al. (1974). Clonal cell lines from the rat central nervous system. Nature, 249(454), 224–227, May 17.

    Article  CAS  PubMed  Google Scholar 

  23. Raghavendra Prasad, H. S., Qi, Z., Srinivasan, K. N., Gopalakrishnakone, P. (2004). Potential effects of tetrodotoxin exposure to human glial cells postulated using microarray approach. Toxicon, 44(6), 597–608, November.

    Article  CAS  PubMed  Google Scholar 

  24. John, V. H., Main, M. J., Powell, A. J., Gladwell, Z. M., Hick, C., Sidhu, H. S., et al. (2004). Heterologous expression and functional analysis of rat Nav1.8 (SNS) voltage-gated sodium channels in the dorsal root ganglion neuroblastoma cell line ND7-23. Neuropharmacology, 46(3), 425–438, Mar.

    Article  CAS  PubMed  Google Scholar 

  25. Kazarinova-Noyes, K., Malhotra, J. D., McEwen, D. P., Mattei, L. N., Berglund, E. O., Ranscht, B., et al. (2001). Contactin associates with Na+ channels and increases their functional expression. Journal of Neuroscience, 21(19), 7517–7525, Oct 1.

    CAS  PubMed  Google Scholar 

  26. Roger, S., Besson, P., & Le Guennec, J. Y. (2003). Involvement of a novel fast inward sodium current in the invasion capacity of a breast cancer cell line. Biochimica et Biophysica Acta, 1616(2), 107–111, Oct 13.

    CAS  PubMed  Google Scholar 

  27. Roger, S., Le Guennec, J. Y., & Besson, P. (2004). Particular sensitivity to calcium channel blockers of the fast inward voltage-dependent sodium current involved in the invasive properties of a metastastic breast cancer cell line. British Journal of Pharmacology, 141(4), 610–615, Feb.

    Article  CAS  PubMed  Google Scholar 

  28. Fraser, S. P., Diss, J. K., Chioni, A. M., Mycielska, M. E., Pan, H., Yamaci, R. F., et al. (2005). Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clinical Cancer Research, 11(15), 5381–5389, Aug 1.

    Article  CAS  PubMed  Google Scholar 

  29. Bennett, E. S., Smith, B. A., & Harper, J. M. (2004). Voltage-gated Na+ channels confer invasive properties on human prostate cancer cells. Pflugers Archive, 447(6), 908–914, Mar.

    Article  CAS  Google Scholar 

  30. Abdul, M., & Hoosein N. (2002). Voltage-gated sodium ion channels in prostate cancer: Expression and activity. Anticancer Research, 22(3), 1727–1730, May–Jun.

    CAS  PubMed  Google Scholar 

  31. Fraser, S. P., Diss, J. K., Lloyd, L. J., Pani, F., Chioni, A. M., George, A. J., et al. (2004). T-lymphocyte invasiveness: Control by voltage-gated Na+ channel activity. FEBS Letters, 569(1–3), 191–194, Jul 2.

    Article  CAS  PubMed  Google Scholar 

  32. Rane, S. G. (2000). The growth regulatory fibroblast IK channel is the prominent electrophysiological feature of rat prostatic cancer cells. Biochemical and Biophysical Research Communications, 269(2), 457–463, Mar 16.

    Article  CAS  PubMed  Google Scholar 

  33. Laniado, M. E., Lalani, E. N., Fraser, S. P., Grimes, J. A., Bhangal, G., Djamgoz, M. B., et al. (1997). Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasion in vitro. American Journal of Pathology, 150(4), 1213–1221, Apr.

    CAS  PubMed  Google Scholar 

  34. Fraser, S. P., Salvador, V., Manning, E. A., Mizal, J., Altun, S., Raza, M., et al. (2003). Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer. I. Lateral motility. Journal of Cellular Physiology, 195(3), 479–487, Jun.

    Article  CAS  PubMed  Google Scholar 

  35. Djamgoz, M. B. A., Mycielska, M., Madeja, Z., Fraser, S. P., & Korohoda, W. (2001). Directional movement of rat prostate cancer cells in direct-current electric field: involvement of voltage-gated Na+ channel activity. Journal of Cell Science, 114(Pt 14), 2697–2705, Jul.

    CAS  PubMed  Google Scholar 

  36. Verrall, J., Fraser, S. P., & Djamgoz, M. B. (1999). Effects of gadolinium ions upon rat prostatic cancer cell lines of markedly different metastatic potential. Cancer Letters, 145(1–2), 79–83, Oct 18.

    Article  CAS  PubMed  Google Scholar 

  37. Abdul, M., & Hoosein N. (2001). Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells. Anticancer Research, 21(3B), 2045–2048, May–Jun.

    CAS  PubMed  Google Scholar 

  38. Sikes, R. A., Anderson, J. D., Hansen, T. P., Choudhury, I. M., Walls, A. M., Brennen, W. N., et al. (2003) Novel ion channel blockers as cytostatic inhibitors of androgen dependent and independent prostate cancer cells. Paper presented at: 94th Annual Meeting; July 11–14, 2003, Washington, District of Columbia.

  39. Lu, Y., Yan, Y., & Wang, X. F. (2004). Antiepileptic drug-induced multidrug resistance P-glycoprotein overexpression in astrocytes cultured from rat brains. Chinese Medical Journal (Engl.), 117(11), 1682–1686, Nov.

    CAS  Google Scholar 

  40. Nozaki-Taguchi, N., Chaplan, S. R., Higuera, E. S., Ajakwe, R. C., & Yaksh, T. L. (2001). Vincristine-induced allodynia in the rat. Pain, 93(1), 69–76, Jul.

    Article  CAS  PubMed  Google Scholar 

  41. Yoshimura, N., Seki, S., Erickson, V., Erickson, K., Kassotakis, L., Novakovic, S., et al. (2001). Suppression of the tetrodotoxin-resistant sodium channel (PN3/SNS): A possible new treatment for bladder pain. Urology, 57(6 Suppl 1), 116–117, Jun.

    Google Scholar 

  42. Mariot, P., Vanoverberghe, K., Lalevee, N., Rossier, M. F., & Prevarskaya, N. (2002). Overexpression of an alpha 1H (Cav3.2) T-type calcium channel during neuroendocrine differentiation of human prostate cancer cells. Journal of Biological Chemistry, 277(13), 10824–10833, Mar 29.

    Article  CAS  PubMed  Google Scholar 

  43. Morton, M. E., Cassidy, T. N., Froehner, S. C., Gilmour, B. P., & Laurens, R. L. (1994). Alpha 1 and alpha 2 Ca2+ channel subunit expression in human neuronal and small cell carcinoma cells. Faseb Journal, 8(11), 884–888, Aug.

    CAS  PubMed  Google Scholar 

  44. Oguro-Okano, M., Griesmann, G. E., Wieben, E. D., Slaymaker, S. J., Snutch, T. P., & Lennon, V. A. (1992). Molecular diversity of neuronal-type calcium channels identified in small cell lung carcinoma. Mayo Clinic Proceedings, 67(12), 1150–1159, Dec.

    CAS  PubMed  Google Scholar 

  45. Su, H., Alroy, G., Kirson, E. D., & Yaari, Y. (2001). Extracellular calcium modulates persistent sodium current-dependent burst-firing in hippocampal pyramidal neurons. Journal of Neuroscience, 21(12):4173–4182, Jun 15.

    CAS  PubMed  Google Scholar 

  46. Huang, J. B., Kindzelskii, A. L., Clark, A. J., & Petty, H. R. (2004). Identification of channels promoting calcium spikes and waves in HT1080 tumor cells: Their apparent roles in cell motility and invasion. Cancer Research, 64(7), 2482–2489, Apr 1.

    Article  CAS  PubMed  Google Scholar 

  47. Schindelholz, B., & Reber, B. F. (2000). L-type Ca2+ channels and purinergic P2X2 cation channels participate in calcium-tyrosine kinase-mediated PC12 growth cone arrest. European Journal of Neuroscience, 12(1), 194–204, Jan.

    Article  CAS  PubMed  Google Scholar 

  48. Firsov, D., Gautschi, I., Merillat, A. M., Rossier, B. C., & Schild, L. (1998). The heterotetrameric architecture of the epithelial sodium channel (ENaC). EMBO Journal, 17(2), 344–352, Jan 15.

    Article  CAS  PubMed  Google Scholar 

  49. Saxena, S., Singh, M., Engisch, K., Fukuda, M., & Kaur, S. (2005). Rab proteins regulate epithelial sodium channel activity in colonic epithelial HT-29 cells. Biochemical and Biophysical Research Communications, 337(4), 1219–1223, Dec 2.

    Article  CAS  PubMed  Google Scholar 

  50. Ismailov, I. I, Berdiev, B. K., Fuller, C. M., Bradford, A. L., Lifton, R. P., Warnock, D. G., et al. (1996). Peptide block of constitutively activated Na+ channels in Liddle’s disease. American Journal of Physiology, 270(1 Pt 1), C214–C223, Jan.

    Google Scholar 

  51. Rohatgi, R., Greenberg, A., Burrow, C. R., Wilson, P. D., & Satlin, L. M. (2003). Na transport in autosomal recessive polycystic kidney disease (ARPKD) cyst lining epithelial cells. Journal of the American Society of Nephrology, 14(4), 827–836, Apr.

    Article  CAS  PubMed  Google Scholar 

  52. Mirshahi, M., Mirshahi, S., Golestaneh, N., Nicolas, C., Mishal, Z., & Agarwal, M. K. (1998). Mineralocorticoid hormone receptor and the epithelial sodium channel in a human leukemic cell line. Endocrine Research, 24(3–4), 455–459, Aug–Nov.

    Article  CAS  PubMed  Google Scholar 

  53. Mirshahi, M., Mirshahi, S., Golestaneh, N., Mishal, Z., Nicolas, C., Hecquet, C., et al. (2000). Demonstration of the mineralocorticoid hormone receptor and action in human leukemic cell lines. Leukemia, 14(6), 1097–1104, Jun.

    Article  CAS  PubMed  Google Scholar 

  54. Mirshahi, M., Golestaneh, N., Valamanesh, F., & Agarwal, M. K. (2000). Paradoxical effects of mineralocorticoids on the ion gated sodium channel in embryologically diverse cells. Biochemical and Biophysical Research Communications, 270(3), 811–815, Apr 21.

    Article  CAS  PubMed  Google Scholar 

  55. Li, W., Duncan, R. L., Karin, N. J., & Farach-Carson, M. C. (1997). 1,25 (OH)2D3 enhances PTH-induced Ca2+ transients in preosteoblasts by activating L-type Ca2+ channels. American Journal of Physiology, 273(3 Pt 1), E599–E605, Sep.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory for Cancer Ontogeny and Therapeutics, University of Delaware, Newark, DE, 19716, USA

    Jamie L. Fiske & Robert A. Sikes

  2. Musculoskeletal Cell Biology Laboratory, Department of Biological Sciences, University of Delaware, Newark, DE, 19716, USA

    Victor P. Fomin & Randall L. Duncan

  3. Department of Chemistry, University of Virginia, Charlottesville, VA, 22903, USA

    Milton L. Brown

  4. Laboratory for Cancer Ontogeny and Therapeutics, University of Delaware, 330 Wolf Hall, Newark, DE, 19716, USA

    Robert A. Sikes

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  1. Jamie L. Fiske
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  3. Milton L. Brown
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  5. Robert A. Sikes
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Correspondence to Robert A. Sikes.

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Fiske, J.L., Fomin, V.P., Brown, M.L. et al. Voltage-sensitive ion channels and cancer. Cancer Metastasis Rev 25, 493–500 (2006). https://doi.org/10.1007/s10555-006-9017-z

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