Review Article | | Peer-Reviewed

Role of Bioelectrical Signaling Networks in Tumor Growth

Received: 16 October 2024     Accepted: 5 November 2024     Published: 28 November 2024
Views:       Downloads:
Abstract

The ion channels are distributed in all cells and promote the rapid influx of ions that underlie the formation of cellular bioelectrical signals. Bioelectrical signals coupled with other regulator mechanisms provide fundamental physiological cellular processes, such as cellular differentiation, proliferation, and apoptosis, which are strongly associated with the manifestation of cancer hallmarks. Alterations in the bioelectrical signaling mechanism underlie the unusual bioelectrical features of cancer cells. Investigating the role of bioelectrical signals in tumor growth provides fundamental insights into cancer diagnosis and tumor-targeted treatment. Hence, this field of research is becoming one of the frontrunners of cancer medicine, and advances in biophysical tools are enabling progress in understanding this biological phenomenon. Recent studies have revealed that bioelectrical signals represent a promising target in cancer therapy. It is becoming increasingly convincing that cancer conditions can be reversed to normal by regulating the bioelectrical signaling mechanism of cells. Herein, we provide a brief review of the role of bioelectrical signals in cancer pathophysiology and provide data on the manipulation of this signaling mechanism as a novel approach to preventing malignant growth.

Published in American Journal of Biomedical and Life Sciences (Volume 12, Issue 5)
DOI 10.11648/j.ajbls.20241205.12
Page(s) 83-92
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Ion Channels, Bioelectrical Signals, Cancer Hallmarks, Spectroscopy, Electrophysiology

References
[1] Funk, R. H. W. & Scholkmann, F. The significance of bioelectricity on all levels of organization of an organism. Part 1: From the subcellular level to cells. Prog. Biophys. Mol. Biol. 177, 185–201 (2023).
[2] Levin, M. Molecular bioelectricity: How endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo. Mol. Biol. Cell 25, 3835–3850 (2014).
[3] Blackiston, D. J., McLaughlin, K. A. & Levin, M. Bioelectric controls of cell proliferation: Ion channels, membrane voltage and the cell cycle. Cell Cycle 8, 3527–3536 (2009).
[4] Sundelacruz, S., Levin, M. & Kaplan, D. L. Role of membrane potential in the regulation of cell proliferation and differentiation. Stem Cell Rev. Reports 5, 231–246 (2009).
[5] Levin, M. Molecular bioelectricity in developmental biology: New tools and recent discoveries. BioEssays 34, 205–217 (2012).
[6] Beane, W. S., Morokuma, J., Lemire, J. M. & Levin, M. Bioelectric signaling regulates head and organ size during planarian regeneration. Pflugers Arch. 140, 313–322 (2013).
[7] Levin, M., Pezzulo, G. & Finkelstein, J. M. Endogenous Bioelectric Signaling Networks: Exploiting Voltage Gradients for Control of Growth and Form. Annu. Rev. Biomed. Eng. 19, 353–387 (2017).
[8] Barghouth, P. G., Thiruvalluvan, M. & Oviedo, N. J. Bioelectrical regulation of cell cycle and the planarian model system. Biochim. Biophys. Acta - Biomembr. 1848, 2629–2637 (2015).
[9] Al Ahmad, M., Al Natour, Z., Mustafa, F. & Rizvi, T. A. Electrical Characterization of Normal and Cancer Cells. IEEE Access 6, 25979–25986 (2018).
[10] Di Gregorio, E. et al. The distinguishing electrical properties of cancer cells. Phys. Life Rev. 43, 139–188 (2022).
[11] Fraser, S. P. et al. Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin. Cancer Res. 11, 5381–5389 (2005).
[12] Payne, S. L., Levin, M. & Oudin, M. J. Bioelectric Control of Metastasis in Solid Tumors. B 1, 114–130 (2019).
[13] Payne, S. L. et al. Potassium channel-driven bioelectric signalling regulates metastasis in triple-negative breast cancer. EBioMedicine 75, 103767 (2022).
[14] Prevarskaya, N., Skryma, R. & Shuba, Y. Ion channels in cancer: Are cancer hallmarks oncochannelopathies? Physiol. Rev. 98, 559–621 (2018).
[15] George, L. F. & Bates, E. A. Mechanisms Underlying Influence of Bioelectricity in Development. Front. Cell Dev. Biol. 10, 1–53 (2022).
[16] Bonnet, S. et al. A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth. Cancer Cell 11, 37–51 (2007).
[17] Silver, B. B. & Nelson, C. M. The bioelectric code: Reprogramming cancer and aging from the interface of mechanical and chemical microenvironments. Front. Cell Dev. Biol. 6, 1–15 (2018).
[18] Sheth, M. & Esfandiari, L. Bioelectric Dysregulation in Cancer Initiation, Promotion, and Progression. Front. Oncol. 12, 1–15 (2022).
[19] Kadir, L. A., Stacey, M. & Barrett-Jolley, R. Emerging roles of the membrane potential: Action beyond the action potential. Front. Physiol. 9, 1–38 (2018).
[20] Jiang, L. H., Adinolfi, E. & Roger, S. Editorial: Ion Channel Signalling in Cancer: From Molecular Mechanisms to Therapeutics. Frontiers in Pharmacology vol. 12 (2021).
[21] Zúñiga, L., Cayo, A., González, W., Vilos, C. & Zúñiga, R. Potassium Channels as a Target for Cancer Therapy: Current Perspectives. Onco. Targets. Ther. 15, 783–797 (2022).
[22] Sakellakis, M., Yoon, S. M., Reet, J. & Chalkias, A. Novel insights into voltage-gated ion channels: Translational breakthroughs in medical oncology. Channels 18, 1–8 (2024).
[23] Moreddu, R. Nanotechnology and Cancer Bioelectricity: Bridging the Gap Between Biology and Translational Medicine. Adv. Sci. 11, 1–25 (2024).
[24] Gururaja Rao, S., Patel, N. J. & Singh, H. Intracellular Chloride Channels: Novel Biomarkers in Diseases. Front. Physiol. 11, 1–18 (2020).
[25] Kofman, K. & Levin, M. Bioelectric pharmacology of cancer: A systematic review of ion channel drugs affecting the cancer phenotype. Prog. Biophys. Mol. Biol. 191, 25–39 (2024).
[26] Altamura, C., Gavazzo, P., Pusch, M. & Desaphy, J. F. Ion Channel Involvement in Tumor Drug Resistance. J. Pers. Med. 12, (2022).
[27] Chen, G. L., Li, J., Zhang, J. & Zeng, B. To Be or Not to Be an Ion Channel: Cryo-EM Structures Have a Say. Cells 12, 1–26 (2023).
[28] Steven M. Chrysafides, Stephen J. Bordes, S. S. Physiology, Resting Potential. (2023).
[29] Raghavan M., Fee D., B. P. Generation and propagation of the action potential. Handb Clin Neurol (2019).
[30] Kabir., M. H. G. R. J. R. Physiology, Action Potential. (2023).
[31] Cervera, J., Pietak, A., Levin, M. & Mafe, S. Bioelectrical coupling in multicellular domains regulated by gap junctions: A conceptual approach. Bioelectrochemistry 123, 45–61 (2018).
[32] Levin, M. Bioelectric signaling: Reprogrammable circuits underlying embryogenesis, regeneration, and cancer. Cell 184, 1971–1989 (2021).
[33] D A Doyle, J Morais Cabral, R A Pfuetzner, A Kuo, J M Gulbis, S L Cohen, B T Chait, R. M. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science (80-. ). 69–77 (1998).
[34] Youxing Jiang, Alice Lee, Jiayun Chen, Martine Cadene, B. T. C. & R. M. Crystal structure and mechanism of a calcium-gated potassium channel. Nature 515–522 (2002).
[35] Peng Yuan, Manuel D Leonetti, Alexander R Pico, Yichun Hsiung, R. M. Structure of the Human BK Channel Ca2+-Activation Apparatus at 3.0 Å Resolution. Science (80-. ). 182–186 (2010).
[36] Yi-Chih Lin, Yusong R Guo, Atsushi Miyagi, Jesper Levring, Roderick MacKinnon, S. S. Force-induced conformational changes in PIEZO1. Nature 230–234 (2019).
[37] Raimund Dutzler 1, Ernest B Campbell, Martine Cadene, Brian T Chait, R. M. X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity. Nat. 287–94 (2002).
[38] Li, W. G. & Xu, T. Le. Emerging approaches to probing ion channel structure and function. Neurosci. Bull. 28, 351–374 (2012).
[39] Bezanilla, F. Ion Channels: From Conductance to Structure. Neuron 60, 456–468 (2008).
[40] Connolly, C. N. Trafficking of 5-HT3 and GABAA receptors (Review). Mol. Membr. Biol. 25, 293–301 (2008).
[41] Sparling, B. A. & Dimauro, E. F. Bioorganic & Medicinal Chemistry Letters Progress in the discovery of small molecule modulators of the Cys-loop superfamily receptors. Bioorg. Med. Chem. Lett. 27, 3207–3218 (2017).
[42] Traynelis, S. F. et al. Glutamate receptor ion channels: Structure, regulation, and function. Pharmacol. Rev. 62, 405–496 (2010).
[43] Pliushcheuskaya, P. & Künze, G. Recent Advances in Computer-Aided Structure-Based Drug Design on Ion Channels. Int. J. Mol. Sci. 24, (2023).
[44] Lau, C., Hunter, M. J., Stewart, A., Perozo, E. & Vandenberg, J. I. Never at rest: insights into the conformational dynamics of ion channels from cryo-electron microscopy. J. Physiol. 596, 1107–1119 (2018).
[45] Hiller, S. & Garces, R. Solution structure of VDAC-1 in detergent micelles. Biol. Chem. 321, 1206–1210 (2009).
[46] Böhm, R. et al. The Structural Basis for Low Conductance in the Membrane Protein VDAC upon β-NADH Binding and Voltage Gating. Structure 28, 206-214.e4 (2020).
[47] Basak, S., Chatterjee, S. & Chakrapani, S. Site directed spin labeling and EPR spectroscopic studies of pentameric ligand-gated ion channels. J. Vis. Exp. 2016, 1–14 (2016).
[48] C Altenbach, T Marti, H G Khorana, W. L. H. Transmembrane protein structure: spin labeling of bacteriorhodopsin mutants. Science (80-. ). 1088–92 (1990).
[49] Gasymov, O. K., Abduragimov, A. R., Yusifov, T. N. & Glasgow, B. J. Binding Studies of Tear Lipocalin: The Role of the Conserved Tryptophan in Maintaining Structure, Stability and Ligand Affinity.
[50] Raghuraman, H., Chatterjee, S. & Das, A. Site-directed fluorescence approaches for dynamic structural biology of membrane peptides and proteins. Front. Mol. Biosci. 6, 1–25 (2019).
[51] Rubaiy, H. N. A Short Guide to Electrophysiology and Ion Channels. 48–67 (2017).
[52] Priest, B. T. et al. Automated Electrophysiology Assays Flowchart Choice of Instrumentation. 1–44 (2017).
[53] Savalli, N., Kondratiev, A., Toro, L. & Olcese, R. Voltage-dependent conformational changes in human Ca2+ and voltage-activated K+ channel, revealed by voltage-clamp fluorometry. Proc. Natl. Acad. Sci. U. S. A. 103, 12619–12624 (2006).
[54] Gandhi Ch., O. R. The voltage-clamp fluorometry technique. Methods Mol Biol. 213–31 (2008).
[55] Savalli, N. et al. The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials. J. Gen. Physiol. 148, 147–159 (2016).
[56] An, K. V, V, K. & V, K. An epilepsy-associated K. 1–10 (2022)
[57] Savalli, N., Kondratiev, A., De Quintana, S. B., Toro, L. & Olcese, R. Modes of operation of the BKCa channel β2 subunit. J. Gen. Physiol. 130, 117–131 (2007).
[58] Savalli, N., Pantazis, A., Yusifov, T., Sigg, D. & Olcese, R. The contribution of RCK domains to human BK channel allosteric activation. J. Biol. Chem. 287, 21741–21750 (2012).
[59] Levin, M. & Ph, D. Bioelectric mechanisms in regeneration. 20, 543–556 (2010).
[60] Levin, M. Bioelectrical approaches to cancer as a problem of the scaling of the cellular self. Prog. Biophys. Mol. Biol. 165, 102–113 (2021).
[61] Catterall, W. A. Voltage-gated sodium channels at 60: Structure, function and pathophysiology. J. Physiol. 590, 2577–2589 (2012).
[62] Brackenbury, W. J. Voltage-gated sodium channels and metastatic disease. 6, 352–361 (2012).
[63] Besson, P. et al. How do voltage-gated sodium channels enhance migration and invasiveness in cancer cells? Biochim. Biophys. Acta - Biomembr. 1848, 2493–2501 (2015).
[64] Brisson, L. et al. NaV1.5 Na+ channels allosterically regulate the NHE-1 exchanger and promote the activity of breast cancer cell invadopodia. J. Cell Sci. 126, 4835–4842 (2013).
[65] Lopez-Charcas, O. et al. The invasiveness of human cervical cancer associated to the function of NaV1.6 channels is mediated by MMP-2 activity. Sci. Rep. 8, 1–16 (2018).
[66] Lopez-Charcas, O. et al. Voltage-Gated Sodium Channel NaV1.5 Controls NHE−1−Dependent Invasive Properties in Colon Cancer Cells. Cancers (Basel). 15, (2023).
[67] Roger, S. et al. Voltage-gated sodium channels potentiate the invasive capacities of human non-small-cell lung cancer cell lines. Int. J. Biochem. Cell Biol. 39, 774–786 (2007).
[68] Djamgoz, M. B. A., Fraser, S. P. & Brackenbury, W. J. In vivo evidence for voltage-gated sodium channel expression in carcinomas and potentiation of metastasis. Cancers (Basel). 11, (2019).
[69] Baptista-Hon, D. T. et al. Potent inhibition by ropivacaine of metastatic colon cancer SW620 cell invasion and NaV1.5 channel function. Br. J. Anaesth. 113, i39–i48 (2014).
[70] Chioni, A. M., Shao, D., Grose, R. & Djamgoz, M. B. A. Protein kinase A and regulation of neonatal Nav1.5 expression in human breast cancer cells: Activity-dependent positive feedback and cellular migration. Int. J. Biochem. Cell Biol. 42, 346–358 (2010).
[71] Djamgoz, M. B. A. Ranolazine: a potential anti-metastatic drug targeting voltage-gated sodium channels. Br. J. Cancer (2024)
[72] Pukkanasut, P. et al. Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells. Cancers vol. 15 (2023).
[73] Bachmann, M. et al. Voltage-Gated Potassium Channels as Regulators of Cell Death. Front. Cell Dev. Biol. 8, 1–17 (2020).
[74] Sakellakis, M. & Chalkias, A. The Role οf Ion Channels in the Development and Progression of Prostate Cancer. Mol. Diagnosis Ther. 27, 227–242 (2023).
[75] Li, M., Tian, P., Zhao, Q., Ma, X. & Zhang, Y. Potassium channels: Novel targets for tumor diagnosis and chemoresistance. Front. Oncol. 12, 1–12 (2023).
[76] Pardo, L. A. Voltage-Gated Potassium Channels Beyond the Action Potential. Bioelectricity 4, 117–125 (2022).
[77] Jehle, J., Schweizer, P. A., Katus, H. A. & Thomas, D. Novel roles for hERG K + channels in cell proliferation and apoptosis. Cell Death Dis. 2, e193-8 (2011).
[78] Stefani, E. et al. Voltage-controlled gating in a large conductance Ca2+-sensitive K+ channel (hslo). Proc. Natl. Acad. Sci. U. S. A. 94, 5427–5431 (1997).
[79] Shangwei Hou, Stefan H. Heinemann, and T. H. Modulation of BKCa channel gating by endogenous signaling molecules. Physiol. 26–35 (2009)
[80] Hoshi, T. & S.H. Heinemann. Modulation of BK Channels by Small Endogenous Molecules and Pharmaceutical Channel Openers. International Review of Neurobiology 193–237 at
[81] Latorre, R. et al. FUNCTIONAL DIVERSITY AND FUNCTIONING BK CHANNEL OPENERS. 39–87 (2024)
[82] A Pantazis, R. O. Biophysics of BK Channel Gating. Int Rev Neurobiol. 1–49 (2016).
[83] Hoshi, T., Pantazis, A. & Olcese, R. Transduction of voltage and Ca2+ signals by Slo1 BK channels. Physiology 28, 172–189 (2013).
[84] Chen, X., Zhang, L., He, L., Zheng, L. & Tuo, B. Potassium channels as novel molecular targets in hepatocellular carcinoma (Review). Oncol. Rep. 50, (2023).
[85] Echeverría, F. et al. Large conductance voltage-and calcium-activated K+ (BK) channel in health and disease. Front. Pharmacol. 1–18 (2024)
[86] Mohr, C. J. et al. Subunits of BK channels promote breast cancer development and modulate responses to endocrine treatment in preclinical models. Br. J. Pharmacol. 179, 2906–2924 (2022).
[87] Bischof, H. et al. mitoBKCa is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming. Elife 12, 1–31 (2023).
[88] Sizemore, G. et al. Opening large-conductance potassium channels selectively induced cell death of triple-negative breast cancer. BMC Cancer 20, 595 (2020).
[89] He, Y. et al. Role for calcium-activated potassium channels (BK) in migration control of human hepatocellular carcinoma cells. J. Cell. Mol. Med. 25, 9685–9696 (2021).
[90] Goda, A. A., Siddique, A. B. & Sayed, K. A. El. The Maxi-K (BK) Channel Antagonist Penitrem A as a Novel Breast Cancer-Targeted Therapeutic. 1–21 (2018)
[91] Haworth, A. S. & Brackenbury, W. J. Emerging roles for multifunctional ion channel auxiliary subunits in cancer. Cell Calcium 80, 125–140 (2019).
[92] Ponnalagu, D. et al. Chloride channel blocker IAA-94 increases myocardial infarction by reducing calcium retention capacity of the cardiac mitochondria. Life Sci (2019)
[93] Saberbaghi, T. et al. Role of Cl− channels in primary brain tumour. Cell Calcium 81, 1–11 (2019).
[94] Jianwen Mao, Jian Yuan, Liwei Wang, Haifeng Zhang, Xiaobao Jin, Jiayong Zhu, Hongzhi Li, Bin Xu, L. C. Tamoxifen inhibits migration of estrogen receptor-negative hepatocellular carcinoma cells by blocking the swelling-activated chloride current. J. Cell. Physiol. 991–1001 (2013).
Cite This Article
  • APA Style

    Yusifov, T., Qudretova, F., Aliyeva, A. (2024). Role of Bioelectrical Signaling Networks in Tumor Growth. American Journal of Biomedical and Life Sciences, 12(5), 83-92. https://doi.org/10.11648/j.ajbls.20241205.12

    Copy | Download

    ACS Style

    Yusifov, T.; Qudretova, F.; Aliyeva, A. Role of Bioelectrical Signaling Networks in Tumor Growth. Am. J. Biomed. Life Sci. 2024, 12(5), 83-92. doi: 10.11648/j.ajbls.20241205.12

    Copy | Download

    AMA Style

    Yusifov T, Qudretova F, Aliyeva A. Role of Bioelectrical Signaling Networks in Tumor Growth. Am J Biomed Life Sci. 2024;12(5):83-92. doi: 10.11648/j.ajbls.20241205.12

    Copy | Download

  • @article{10.11648/j.ajbls.20241205.12,
      author = {Taleh Yusifov and Fidan Qudretova and Aysel Aliyeva},
      title = {Role of Bioelectrical Signaling Networks in Tumor Growth
    },
      journal = {American Journal of Biomedical and Life Sciences},
      volume = {12},
      number = {5},
      pages = {83-92},
      doi = {10.11648/j.ajbls.20241205.12},
      url = {https://doi.org/10.11648/j.ajbls.20241205.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbls.20241205.12},
      abstract = {The ion channels are distributed in all cells and promote the rapid influx of ions that underlie the formation of cellular bioelectrical signals. Bioelectrical signals coupled with other regulator mechanisms provide fundamental physiological cellular processes, such as cellular differentiation, proliferation, and apoptosis, which are strongly associated with the manifestation of cancer hallmarks. Alterations in the bioelectrical signaling mechanism underlie the unusual bioelectrical features of cancer cells. Investigating the role of bioelectrical signals in tumor growth provides fundamental insights into cancer diagnosis and tumor-targeted treatment. Hence, this field of research is becoming one of the frontrunners of cancer medicine, and advances in biophysical tools are enabling progress in understanding this biological phenomenon. Recent studies have revealed that bioelectrical signals represent a promising target in cancer therapy. It is becoming increasingly convincing that cancer conditions can be reversed to normal by regulating the bioelectrical signaling mechanism of cells. Herein, we provide a brief review of the role of bioelectrical signals in cancer pathophysiology and provide data on the manipulation of this signaling mechanism as a novel approach to preventing malignant growth.
    },
     year = {2024}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Role of Bioelectrical Signaling Networks in Tumor Growth
    
    AU  - Taleh Yusifov
    AU  - Fidan Qudretova
    AU  - Aysel Aliyeva
    Y1  - 2024/11/28
    PY  - 2024
    N1  - https://doi.org/10.11648/j.ajbls.20241205.12
    DO  - 10.11648/j.ajbls.20241205.12
    T2  - American Journal of Biomedical and Life Sciences
    JF  - American Journal of Biomedical and Life Sciences
    JO  - American Journal of Biomedical and Life Sciences
    SP  - 83
    EP  - 92
    PB  - Science Publishing Group
    SN  - 2330-880X
    UR  - https://doi.org/10.11648/j.ajbls.20241205.12
    AB  - The ion channels are distributed in all cells and promote the rapid influx of ions that underlie the formation of cellular bioelectrical signals. Bioelectrical signals coupled with other regulator mechanisms provide fundamental physiological cellular processes, such as cellular differentiation, proliferation, and apoptosis, which are strongly associated with the manifestation of cancer hallmarks. Alterations in the bioelectrical signaling mechanism underlie the unusual bioelectrical features of cancer cells. Investigating the role of bioelectrical signals in tumor growth provides fundamental insights into cancer diagnosis and tumor-targeted treatment. Hence, this field of research is becoming one of the frontrunners of cancer medicine, and advances in biophysical tools are enabling progress in understanding this biological phenomenon. Recent studies have revealed that bioelectrical signals represent a promising target in cancer therapy. It is becoming increasingly convincing that cancer conditions can be reversed to normal by regulating the bioelectrical signaling mechanism of cells. Herein, we provide a brief review of the role of bioelectrical signals in cancer pathophysiology and provide data on the manipulation of this signaling mechanism as a novel approach to preventing malignant growth.
    
    VL  - 12
    IS  - 5
    ER  - 

    Copy | Download

Author Information
  • Sections