Skip to main content
SpringerLink
Log in

Ion Transport and Radioresistance

  • Chapter
  • First Online:
Targets of Cancer Diagnosis and Treatment

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 183))

Abstract

Neoplastic transformation is associated with alterations of the ion transports across plasma and intracellular membranes. These alterations are crucial elements of the phenotypical reprogramming of the transformed cells and may promote adaptation to hypoxia, malignant progression, tumor spreading and metastasis, as well as therapy resistance. The present review article focuses on ion transport processes in tumor cells that are induced by ionizing radiation and that contribute to radioresistance and therapy failure. In particular, this article introduces radiogenic ion transports across plasma and mitochondrial membranes and discusses their functional significance for cell cycle control, DNA repair, accelerated repopulation, cell migration and metastasis, metabolic reprogramming, adaptation to hypoxia, and radiogenic formation of reactive oxygen species.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ΔΨm:

Inner mitochondrial membrane potential

•O2−:

Superoxide anion radical

AMPK:

5′ Adenosine monophosphate-activated protein kinase

ATM:

Protein kinase ataxia-telangiectasia mutated

CaMKIIs:

Isoforms of the Ca2+/calmodulin-dependent kinase-II

CLIC1:

Chloride intracellular channel-1

CXCR4:

C-X-C motif chemokine receptor-4

DSBs:

DNA double-strand breaks

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial–mesenchymal transition

ERK:

Extracellular signal-regulated kinase

GMT:

Glial-mesenchymal transition

GSCs:

Glioblastoma stem cells

HIF-1α:

Hypoxia-inducible factor-1α

KATP:

ATP-sensitive potassium channel

KCa:

Calcium-activated potassium channel

Kv:

Voltage-gated potassium channel

MnSOD:

Mitochondrial manganese superoxide dismutase (SOD2)

MPT:

Mitochondrial membrane permeability transition pore

mt :

Mitochondrial

Nav:

Voltage-gated sodium channel

Pyk2 :

Focal adhesion kinase-2

ROS:

Reactive oxygen species

SDF1:

Stromal cell-derived factor-1 (CXCL12)

TRPM2/8:

Member 2/8 of the melastatin family of transient receptor potential nonselective cation channels

TRPV1/5/6:

Member 1/5/6 of the vanilloid family of transient receptor potential nonselective cation channels

UCP2/3:

Uncoupling protein-2/3

VDAC1:

Voltage-gated anion channel-1

Vm:

Membrane potential

References

  • Anoopkumar-Dukie S, Conere T, Sisk GD et al (2009) Mitochondrial modulation of oxygen-dependent radiosensitivity in some human tumour cell lines. Br J Radiol 82:847–854

    CAS  PubMed  Google Scholar 

  • Archer SL, Gomberg-Maitland M, Maitland ML et al (2008) Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol 294:H570–H578

    CAS  PubMed  Google Scholar 

  • Arif T, Stern O, Pittala S et al (2019) Rewiring of cancer cell metabolism by mitochondrial VDAC1 depletion results in time-dependent tumor reprogramming: Glioblastoma as a proof of concept. Cell 8:1330

    Google Scholar 

  • Arthur GK, Duffy SM, Roach KM et al (2015) KCa3.1 K+ channel expression and function in human bronchial epithelial cells. PLoS One 10:e0145259

    PubMed  PubMed Central  Google Scholar 

  • Ataga KI, Smith WR, De Castro LM et al (2008) Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood 111:3991–3997

    CAS  PubMed  Google Scholar 

  • Averaimo S, Milton RH, Duchen MR et al (2010) Chloride intracellular channel 1 (CLIC1): sensor and effector during oxidative stress. FEBS Lett 584:2076–2084

    CAS  PubMed  Google Scholar 

  • Baffy G (2017) Mitochondrial uncoupling in cancer cells: liabilities and opportunities. Biochim Biophys Acta Bioenerg 1858:655–664

    CAS  PubMed  Google Scholar 

  • Bauer TM, Murphy E (2020) Role of mitochondrial calcium and the permeability transition pore in regulating cell death. Circ Res 126:280–293

    CAS  PubMed  PubMed Central  Google Scholar 

  • Birch JL, Strathdee K, Gilmour L et al (2018) A novel small-molecule inhibitor of MRCK prevents radiation-driven invasion in Glioblastoma. Cancer Res 78:6509–6522

    CAS  PubMed  Google Scholar 

  • Bouchard G, Therriault H, Geha S et al (2017) Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model. Br J Cancer 116:479–488

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brahimi-Horn MC, Ben-Hail D, Ilie M et al (2012) Expression of a truncated active form of VDAC1 in lung cancer associates with hypoxic cell survival and correlates with progression to chemotherapy resistance. Cancer Res 72:2140–2150

    CAS  PubMed  Google Scholar 

  • Braun N, Klumpp D, Hennenlotter J et al (2015) UCP-3 uncoupling protein confers hypoxia resistance to renal epithelial cells and is upregulated in renal cell carcinoma. Sci Rep 5:13450

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brisson L, Gillet L, Calaghan S et al (2011) NaV1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H+ efflux in caveolae. Oncogene 30:2070–2076

    CAS  PubMed  Google Scholar 

  • Brisson L, Driffort V, Benoist L et al (2013) 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

    CAS  PubMed  Google Scholar 

  • Britschgi A, Bill A, Brinkhaus H et al (2013) Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling. Proc Natl Acad Sci U S A 110:E1026–E1034

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brown A, Geiger H (2018) Chromosome integrity checkpoints in stem and progenitor cells: transitions upon differentiation, pathogenesis, and aging. Cell Mol Life Sci 75:3771–3779

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cadenas S (2018) Mitochondrial uncoupling, ROS generation and cardioprotection. Biochim Biophys Acta Bioenerg 1859:940–950

    CAS  PubMed  Google Scholar 

  • Campbell TM, Main MJ, Fitzgerald EM (2013) Functional expression of the voltage-gated Na+-channel Nav1.7 is necessary for EGF-mediated invasion in human non-small cell lung cancer cells. J Cell Sci 126:4939–4949

    CAS  PubMed  Google Scholar 

  • Chao HX, Poovey CE, Privette AA et al (2017) Orchestration of DNA damage checkpoint dynamics across the human cell cycle. Cell Syst 5:445–459.e445

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen JM, Sepramaniam S, Armugam A et al (2008) Water and ion channels: crucial in the initiation and progression of apoptosis in central nervous system? Curr Neuropharmacol 6:102–116

    CAS  Google Scholar 

  • Chen TJ, He HL, Shiue YL et al (2018) High chloride channel accessory 1 expression predicts poor prognoses in patients with rectal cancer receiving chemoradiotherapy. Int J Med Sci 15:1171–1178

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng Y, Debska-Vielhaber G, Siemen D (2010) Interaction of mitochondrial potassium channels with the permeability transition pore. FEBS Lett 584:2005–2012

    CAS  PubMed  Google Scholar 

  • Cloos CR, Daniels DH, Kalen A et al (2009) Mitochondrial DNA depletion induces radioresistance by suppressing G2 checkpoint activation in human pancreatic cancer cells. Radiat Res 171:581–587

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cone CD Jr, Cone CM (1976) Induction of mitosis in mature neurons in central nervous system by sustained depolarization. Science 192:155–158

    CAS  PubMed  Google Scholar 

  • Cone CD Jr, Tongier M Jr (1971) Control of somatic cell mitosis by simulated changes in the transmembrane potential level. Oncology 25:168–182

    CAS  PubMed  Google Scholar 

  • Coultrap SJ, Bayer KU (2012) CaMKII regulation in information processing and storage. Trends Neurosci 35:607–618

    CAS  PubMed  PubMed Central  Google Scholar 

  • Crottes D, Jan LY (2019) The multifaceted role of TMEM16A in cancer. Cell Calcium 82:102050

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cruz-Gregorio A, Martinez-Ramirez I, Pedraza-Chaverri J et al (2019) Reprogramming of energy metabolism in response to radiotherapy in head and neck squamous cell carcinoma. Cancers (Basel) 11:182

    Google Scholar 

  • Cuddapah VA, Sontheimer H (2010) Molecular interaction and functional regulation of ClC-3 by Ca2+/calmodulin-dependent protein kinase II (CaMKII) in human malignant glioma. J Biol Chem 285:11188–11196

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cuddapah VA, Habela CW, Watkins S et al (2012) Kinase activation of ClC-3 accelerates cytoplasmic condensation during mitotic cell rounding. Am J Physiol Cell Physiol 302:C527–C538

    CAS  PubMed  Google Scholar 

  • Cuddapah VA, Turner KL, Seifert S et al (2013) Bradykinin-induced chemotaxis of human gliomas requires the activation of KCa3.1 and ClC-3. J Neurosci 33:1427–1440

    CAS  PubMed  PubMed Central  Google Scholar 

  • D’alessandro G, Catalano M, Sciaccaluga M et al (2013) KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in vivo. Cell Death Dis 4:e773

    PubMed  PubMed Central  Google Scholar 

  • D’alessandro G, Monaco L, Catacuzzeno L et al (2019) Radiation increases functional KCa3.1 expression and invasiveness in glioblastoma. Cancers (Basel) 11:279

    Google Scholar 

  • Davies A, Hendrich J, Van Minh AT et al (2007) Functional biology of the alpha2delta subunits of voltage-gated calcium channels. Trends Pharmacol Sci 28:220–228

    CAS  PubMed  Google Scholar 

  • Davis FM, Peters AA, Grice DM et al (2012) Non-stimulated, agonist-stimulated and store-operated Ca2+ influx in MDA-MB-468 breast cancer cells and the effect of EGF-induced EMT on calcium entry. PLoS One 7:e36923

    CAS  PubMed  PubMed Central  Google Scholar 

  • Denko NC (2008) Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 8:705–713

    CAS  PubMed  Google Scholar 

  • Dittmann K, Mayer C, Kehlbach R et al (2008) Radiation-induced caveolin-1 associated EGFR internalization is linked with nuclear EGFR transport and activation of DNA-PK. Mol Cancer 7:69

    PubMed  PubMed Central  Google Scholar 

  • Dittmann K, Mayer C, Kehlbach R et al (2009) Radiation-induced lipid peroxidation activates SRC kinase and triggers nuclear EGFR transport. Radiother Oncol 92:379–382

    CAS  PubMed  Google Scholar 

  • Dittmann K, Mayer C, Rodemann HP et al (2013) EGFR cooperates with glucose transporter SGLT1 to enable chromatin remodeling in response to ionizing radiation. Radiother Oncol 107:247–251

    CAS  PubMed  Google Scholar 

  • Dittmann K, Mayer C, Paasch A et al (2015) Nuclear EGFR renders cells radio-resistant by binding mRNA species and triggering a metabolic switch to increase lactate production. Radiother Oncol 116:431–437

    CAS  PubMed  Google Scholar 

  • Djamgoz MBA, Fraser SP, Brackenbury WJ (2019) In vivo evidence for voltage-gated Sodium Channel expression in carcinomas and potentiation of metastasis. Cancers (Basel) 11:1675

    CAS  Google Scholar 

  • Driffort V, Gillet L, Bon E et al (2014) Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization. Mol Cancer 13:264

    PubMed  PubMed Central  Google Scholar 

  • Dupre AM, Hempling HG (1978) Osmotic properties of Ehrlich ascites tumor cells during the cell cycle. J Cell Physiol 97:381–396

    CAS  PubMed  Google Scholar 

  • Eckert F, Schilbach K, Klumpp L et al (2018) Potential role of CXCR4 targeting in the context of radiotherapy and immunotherapy of cancer. Front Immunol 9:3018

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eckert F, Zwirner K, Boeke S et al (2019) Rationale for combining radiotherapy and immune checkpoint inhibition for patients with hypoxic tumors. Front Immunol 10:407

    CAS  PubMed  PubMed Central  Google Scholar 

  • Edalat L, Stegen B, Klumpp L et al (2016) BK K+ channel blockade inhibits radiation-induced migration/brain infiltration of glioblastoma cells. Oncotarget 7:14259–14278

    PubMed  PubMed Central  Google Scholar 

  • Eke I, Storch K, Kastner I et al (2012) Three-dimensional invasion of human glioblastoma cells remains unchanged by X-ray and carbon ion irradiation in vitro. Int J Radiat Oncol Biol Phys 84:e515–e523

    PubMed  Google Scholar 

  • Ewing D (1998) The oxygen fixation hypothesis: a reevaluation. Am J Clin Oncol 21:355–361

    CAS  PubMed  Google Scholar 

  • Faubert B, Solmonson A, Deberardinis RJ (2020) Metabolic reprogramming and cancer progression. Science 368(6487):eaaw5473

    Google Scholar 

  • Foller M, Bobbala D, Koka S et al (2010) Functional significance of the intermediate conductance Ca2+-activated K+ channel for the short-term survival of injured erythrocytes. Pflugers Arch 460:1029–1044

    PubMed  Google Scholar 

  • Fraser SP, Diss JK, Chioni AM et al (2005) Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin Cancer Res 11:5381–5389

    CAS  PubMed  Google Scholar 

  • Fu C, Cao CM, Xia Q et al (2003) Reactive oxygen species and mitochondrial KATP-sensitive channels mediated cardioprotection induced by TNF-alpha during hypoxia and reoxygenation. Sheng Li Xue Bao 55:284–289

    CAS  PubMed  Google Scholar 

  • Gibhardt CS, Roth B, Schroeder I et al (2015) X-ray irradiation activates K+ channels via H2O2 signaling. Sci Rep 5:13861

    PubMed  PubMed Central  Google Scholar 

  • Gillet L, Roger S, Besson P et al (2009) Voltage-gated sodium channel activity promotes cysteine cathepsin-dependent invasiveness and colony growth of human cancer cells. J Biol Chem 284:8680–8691

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Gonzalez L, Gonzalez-Ramirez R, Flores A et al (2019) Epidermal growth factor potentiates migration of MDA-MB 231 breast cancer cells by increasing NaV1.5 channel expression. Oncology 97:373–382

    CAS  PubMed  Google Scholar 

  • Gopel SO, Kanno T, Barg S et al (2000) Patch-clamp characterisation of somatostatin-secreting -cells in intact mouse pancreatic islets. J Physiol 528:497–507

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gu XQ, Siemen D, Parvez S et al (2007) Hypoxia increases BK channel activity in the inner mitochondrial membrane. Biochem Biophys Res Commun 358:311–316

    CAS  PubMed  Google Scholar 

  • Gu XQ, Pamenter ME, Siemen D et al (2014) Mitochondrial but not plasmalemmal BK channels are hypoxia-sensitive in human glioma. Glia 62:504–513

    PubMed  Google Scholar 

  • Gueguinou M, Chantome A, Fromont G et al (1843) KCa and Ca2+ channels: the complex thought. Biochim Biophys Acta:2322–2333

    Google Scholar 

  • Guo L, Tang X, Tian H et al (2008) Subacute hypoxia suppresses Kv3.4 channel expression and whole-cell K+ currents through endogenous 15-hydroxyeicosatetraenoic acid in pulmonary arterial smooth muscle cells. Eur J Pharmacol 587:187–195

    CAS  PubMed  Google Scholar 

  • Heise N, Palme D, Misovic M et al (2010) Non-selective cation channel-mediated Ca2+-entry and activation of Ca2+/calmodulin-dependent kinase II contribute to G2/M cell cycle arrest and survival of irradiated leukemia cells. Cell Physiol Biochem 26:597–608

    CAS  PubMed  Google Scholar 

  • Holley AK, Miao L, St Clair DK et al (2014) Redox-modulated phenomena and radiation therapy: the central role of superoxide dismutases. Antioxid Redox Signal 20:1567–1589

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hu J, Qin K, Zhang Y et al (2011) Downregulation of transcription factor Oct4 induces an epithelial-to-mesenchymal transition via enhancement of Ca2+ influx in breast cancer cells. Biochem Biophys Res Commun 411:786–791

    CAS  PubMed  Google Scholar 

  • Huang L, Li B, Tang S et al (2015) Mitochondrial KATP channels control glioma radioresistance by regulating ROS-induced ERK activation. Mol Neurobiol 52:626–637

    CAS  PubMed  Google Scholar 

  • Huang Y, Fliegert R, Guse AH et al (2020) A structural overview of the ion channels of the TRPM family. Cell Calcium 85:102111

    CAS  PubMed  Google Scholar 

  • Huber SM (2013) Oncochannels. Cell Calcium 53:241–255

    CAS  PubMed  Google Scholar 

  • Huber SM, Tschop J, Braun GS et al (1999) Bradykinin-stimulated Cl− secretion in T84 cells. Role of Ca2+-activated hSK4-like K+ channels. Pflugers Arch 438:53–60

    CAS  PubMed  Google Scholar 

  • Huber SM, Misovic M, Mayer C et al (2012) EGFR-mediated stimulation of sodium/glucose cotransport promotes survival of irradiated human A549 lung adenocarcinoma cells. Radiother Oncol 103:373–379

    CAS  PubMed  Google Scholar 

  • Huber SM, Butz L, Stegen B et al (2013) Ionizing radiation, ion transports, and radioresistance of cancer cells. Front Physiol 4:212

    PubMed  PubMed Central  Google Scholar 

  • Jentsch TJ, Pusch M (2018) CLC chloride channels and transporters: structure, function, physiology, and disease. Physiol Rev 98:1493–1590

    CAS  PubMed  Google Scholar 

  • Jesse RH, Lindberg RD (1975) The efficacy of combining radiation therapy with a surgical procedure in patients with cervical metastasis from squamous cancer of the oropharynx and hypopharynx. Cancer 35:1163–1166

    CAS  PubMed  Google Scholar 

  • Kaczmarek LK, Zhang Y (2017) Kv3 channels: enablers of rapid firing, neurotransmitter release, and neuronal endurance. Physiol Rev 97:1431–1468

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kandasamy SB, Howerton TC, Hunt WA (1991) Reductions in calcium uptake induced in rat brain synaptosomes by ionizing radiation. Radiat Res 125:158–162

    CAS  PubMed  Google Scholar 

  • Kaplan HS, Murphy ED (1949) The effect of local roentgen irradiation on the biological behavior of a transplantable mouse carcinoma; increased frequency of pulmonary metastasis. J Natl Cancer Inst 9:407–413

    CAS  PubMed  Google Scholar 

  • Kim JS, Chang JW, Yun HS et al (2010) Chloride intracellular channel 1 identified using proteomic analysis plays an important role in the radiosensitivity of HEp-2 cells via reactive oxygen species production. Proteomics 10:2589–2604

    CAS  PubMed  Google Scholar 

  • Kim MJ, Kim RK, Yoon CH et al (2011) Importance of PKCdelta signaling in fractionated-radiation-induced expansion of glioma-initiating cells and resistance to cancer treatment. J Cell Sci 124:3084–3094

    CAS  PubMed  Google Scholar 

  • Kim W, Lee S, Seo D et al (2019) Cellular stress responses in radiotherapy. Cell 8:1105

    CAS  Google Scholar 

  • Kizub IV, Pavlova OO, Ivanova IV et al (2010) Protein kinase C-dependent inhibition of BKCa current in rat aorta smooth muscle cells following gamma-irradiation. Int J Radiat Biol 86:291–299

    CAS  PubMed  Google Scholar 

  • Klumpp D, Misovic M, Szteyn K et al (2016a) Targeting TRPM2 channels impairs radiation-induced cell cycle arrest and fosters cell death of T cell leukemia cells in a Bcl-2-dependent manner. Oxidative Med Cell Longev 2016:8026702

    Google Scholar 

  • Klumpp L, Sezgin EC, Eckert F et al (2016b) Ion channels in brain metastasis. Int J Mol Sci 17:1513

    Google Scholar 

  • Klumpp D, Frank SC, Klumpp L et al (2017) TRPM8 is required for survival and radioresistance of glioblastoma cells. Oncotarget 8:95896–95913

    PubMed  PubMed Central  Google Scholar 

  • Klumpp L, Sezgin EC, Skardelly M et al (2018) KCa3.1 channels and glioblastoma: in vitro studies. Curr Neuropharmacol 16:627–635

    CAS  PubMed  PubMed Central  Google Scholar 

  • Krebs C (1929) Effect of roentgen irradiation on the interrelation between malignant tumors and their hosts. Acta Radiol Supp 8:1–133

    Google Scholar 

  • Kulawiak B, Kudin AP, Szewczyk A et al (2008) BK channel openers inhibit ROS production of isolated rat brain mitochondria. Exp Neurol 212:543–547

    CAS  PubMed  Google Scholar 

  • Kunzelmann K, Ousingsawat J, Benedetto R et al (2019) Contribution of Anoctamins to cell survival and cell death. Cancers (Basel) 11:382

    Google Scholar 

  • Kyrychenko S, Tishkin S, Dosenko V et al (2012) The BK(Ca) channels deficiency as a possible reason for radiation-induced vascular hypercontractility. Vasc Pharmacol 56:142–149

    CAS  Google Scholar 

  • Lang F, Pelzl L, Hauser S et al (2018) To die or not to die SGK1-sensitive ORAI/STIM in cell survival. Cell Calcium 74:29–34

    CAS  PubMed  Google Scholar 

  • Leach JK, Van Tuyle G, Lin PS et al (2001) Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res 61:3894–3901

    CAS  PubMed  Google Scholar 

  • Leanza L, O'reilly P, Doyle A et al (2014) Correlation between potassium channel expression and sensitivity to drug-induced cell death in tumor cell lines. Curr Pharm Des 20:189–200

    CAS  PubMed  Google Scholar 

  • Li F, Sonveaux P, Rabbani ZN et al (2007) Regulation of HIF-1alpha stability through S-nitrosylation. Mol Cell 26:63–74

    PubMed  PubMed Central  Google Scholar 

  • Lin S, Lv Y, Xu J et al (2019) Over-expression of Nav1.6 channels is associated with lymph node metastases in colorectal cancer. World J Surg Oncol 17:175

    PubMed  PubMed Central  Google Scholar 

  • Littler DR, Harrop SJ, Goodchild SC et al (2010) The enigma of the CLIC proteins: ion channels, redox proteins, enzymes, scaffolding proteins? FEBS Lett 584:2093–2101

    CAS  PubMed  Google Scholar 

  • Liu W, Lu M, Liu B et al (2012) Inhibition of Ca2+-activated Cl− channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma. Cancer Lett 326:41–51

    CAS  PubMed  Google Scholar 

  • Liu J, Chen Y, Shuai S et al (2014) TRPM8 promotes aggressiveness of breast cancer cells by regulating EMT via activating AKT/GSK-3beta pathway. Tumour Biol 35:8969–8977

    CAS  PubMed  Google Scholar 

  • Mahdi SH, Cheng H, Li J et al (2015) The effect of TGF-beta-induced epithelial-mesenchymal transition on the expression of intracellular calcium-handling proteins in T47D and MCF-7 human breast cancer cells. Arch Biochem Biophys 583:18–26

    CAS  PubMed  Google Scholar 

  • Maldonado EN (2017) VDAC-tubulin, an anti-Warburg pro-oxidant switch. Front Oncol 7:4

    PubMed  PubMed Central  Google Scholar 

  • Martin OA, Anderson RL, Russell PA et al (2014) Mobilization of viable tumor cells into the circulation during radiation therapy. Int J Radiat Oncol Biol Phys 88:395–403

    PubMed  Google Scholar 

  • Masumoto K, Tsukimoto M, Kojima S (2013) Role of TRPM2 and TRPV1 cation channels in cellular responses to radiation-induced DNA damage. Biochim Biophys Acta 1830:3382–3390

    CAS  PubMed  Google Scholar 

  • Matsuya Y, Ohtsubo Y, Tsutsumi K et al (2014) Quantitative estimation of DNA damage by photon irradiation based on the microdosimetric-kinetic model. J Radiat Res 55:484–493

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mazure NM (2016) News about VDAC1 in hypoxia. Front Oncol 6:193

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meng Y, Xu X, Luan H et al (2019) The progress and development of GLUT1 inhibitors targeting cancer energy metabolism. Future Med Chem 11:2333–2352

    CAS  PubMed  Google Scholar 

  • Miranda-Goncalves V, Granja S, Martinho O et al (2016) Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas. Oncotarget 7:46335–46353

    PubMed  PubMed Central  Google Scholar 

  • Mohammed FH, Khajah MA, Yang M et al (2016) Blockade of voltage-gated sodium channels inhibits invasion of endocrine-resistant breast cancer cells. Int J Oncol 48:73–83

    CAS  PubMed  Google Scholar 

  • Mohr CJ, Gross D, Sezgin EC et al (2019) KCa3.1 channels confer radioresistance to breast cancer cells. Cancers (Basel) 11:1285

    Google Scholar 

  • Munro TR (1970) The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts. Radiat Res 42:451–470

    CAS  PubMed  Google Scholar 

  • Nagy JA, Chang SH, Dvorak AM et al (2009) Why are tumour blood vessels abnormal and why is it important to know? Br J Cancer 100:865–869

    CAS  PubMed  PubMed Central  Google Scholar 

  • Neher E, Sakmann B (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260:799–802

    CAS  PubMed  Google Scholar 

  • Nelson M, Yang M, Dowle AA et al (2015a) The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis. Mol Cancer 14:13

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson M, Yang M, Millican-Slater R et al (2015b) Nav1.5 regulates breast tumor growth and metastatic dissemination in vivo. Oncotarget 6:32914–32929

    PubMed  PubMed Central  Google Scholar 

  • Nishino K, Tanamachi K, Nakanishi Y et al (2016) Radiosensitizing effect of TRPV1 channel inhibitors in cancer cells. Biol Pharm Bull 39:1224–1230

    CAS  PubMed  Google Scholar 

  • Noyer L, Grolez GP, Prevarskaya N et al (2018) TRPM8 and prostate: a cold case? Pflugers Arch 470:1419–1429

    CAS  PubMed  Google Scholar 

  • Ogawa K, Utsunomiya T, Mimori K et al (2006) Differential gene expression profiles of radioresistant pancreatic cancer cell lines established by fractionated irradiation. Int J Oncol 28:705–713

    CAS  PubMed  Google Scholar 

  • Palme D, Misovic M, Schmid E et al (2013) Kv3.4 potassium channel-mediated electrosignaling controls cell cycle and survival of irradiated leukemia cells. Pflugers Arch 465:1209–1221

    CAS  PubMed  Google Scholar 

  • Palme D, Misovic M, Ganser K et al (2020) hERG K+ channels promote survival of irradiated leukemia cells. Front Pharmacol 11:489

    CAS  PubMed  PubMed Central  Google Scholar 

  • Peitzsch C, Perrin R, Hill RP et al (2014) Hypoxia as a biomarker for radioresistant cancer stem cells. Int J Radiat Biol 90:636–652

    CAS  PubMed  Google Scholar 

  • Peng JB, Suzuki Y, Gyimesi G et al (2018) TRPV5 and TRPV6 calcium-selective channels. In: Kozak JA, Putney JW Jr (eds) Calcium entry channels in non-excitable cells. CRC Press, Taylor & Francis Group, Boca Raton, pp 241–274

    Google Scholar 

  • Proudfoot JM, Murrey MW, Mclean S et al (2018) F2-isoprostanes affect macrophage migration and CSF-1 signalling. Free Radic Biol Med 126:142–152

    CAS  PubMed  Google Scholar 

  • Qu Y, Zhang H, Zhao S et al (2010) The effect on radioresistance of manganese superoxide dismutase in nasopharyngeal carcinoma. Oncol Rep 23:1005–1011

    CAS  PubMed  Google Scholar 

  • Ravi M, Paramesh V, Kaviya SR et al (2015) 3D cell culture systems: advantages and applications. J Cell Physiol 230:16–26

    CAS  PubMed  Google Scholar 

  • Redfern A, Agarwal V, Thompson EW (2019) Hypoxia as a signal for prison breakout in cancer. Curr Opin Clin Nutr Metab Care 22:250–263

    PubMed  Google Scholar 

  • Reisz JA, Bansal N, Qian J et al (2014) Effects of ionizing radiation on biological molecules--mechanisms of damage and emerging methods of detection. Antioxid Redox Signal 21:260–292

    CAS  PubMed  PubMed Central  Google Scholar 

  • Richardson RB, Harper ME (2016) Mitochondrial stress controls the radiosensitivity of the oxygen effect: implications for radiotherapy. Oncotarget 7:21469–21483

    PubMed  PubMed Central  Google Scholar 

  • Rodemann HP, Dittmann K, Toulany M (2007) Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol 83:781–791

    CAS  PubMed  Google Scholar 

  • Roth B, Gibhardt CS, Becker P et al (2015) Low-dose photon irradiation alters cell differentiation via activation of hIK channels. Pflugers Arch 467:1835–1849

    CAS  PubMed  Google Scholar 

  • Ruggieri P, Mangino G, Fioretti B et al (2012) The inhibition of KCa3.1 channels activity reduces cell motility in glioblastoma derived cancer stem cells. PLoS One 7:e47825

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ruoslahti E (1996) Brain extracellular matrix. Glycobiology 6:489–492

    CAS  PubMed  Google Scholar 

  • Sala-Rabanal M, Yurtsever Z, Nichols CG et al (2015) Secreted CLCA1 modulates TMEM16A to activate Ca2+-dependent chloride currents in human cells. Elife 4:e05875

    Google Scholar 

  • Sanguinetti MC (2010) HERG1 channelopathies. Pflugers Arch 460:265–276

    CAS  PubMed  Google Scholar 

  • Sausbier M, Hu H, Arntz C et al (2004) Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2+-activated K+ channel deficiency. Proc Natl Acad Sci U S A 101:9474–9478

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schumann T, Konig J, Henke C et al (2020) Solute carrier transporters as potential targets for the treatment of metabolic disease. Pharmacol Rev 72:343–379

    CAS  PubMed  Google Scholar 

  • Sheldon PW, Fowler JF (1976) The effect of low-dose pre-operative X-irradiation of implanted mouse mammary carcinomas on local recurrence and metastasis. Br J Cancer 34:401–407

    CAS  PubMed  PubMed Central  Google Scholar 

  • Si H, Heyken WT, Wolfle SE et al (2006) Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel. Circ Res 99:537–544

    CAS  PubMed  Google Scholar 

  • Skonieczna M, Cieslar-Pobuda A, Saenko Y et al (2017) The impact of DIDS-induced inhibition of voltage-dependent anion channels (VDAC) on cellular response of Lymphoblastoid cells to ionizing radiation. Med Chem 13:477–483

    CAS  PubMed  Google Scholar 

  • Soloviev A, Tishkin S, Ivanova I et al (2009) Functional and molecular consequences of ionizing irradiation on large conductance Ca2+-activated K+ channels in rat aortic smooth muscle cells. Life Sci 84:164–171

    CAS  PubMed  Google Scholar 

  • Soltysinska E, Bentzen BH, Barthmes M et al (2014) KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury. PLoS One 9:e103402

    PubMed  PubMed Central  Google Scholar 

  • Song MS, Ryu PD, Lee SY (2017) Kv3.4 is modulated by HIF-1alpha to protect SH-SY5Y cells against oxidative stress-induced neural cell death. Sci Rep 7:2075

    PubMed  PubMed Central  Google Scholar 

  • Sontheimer H (2008) An unexpected role for ion channels in brain tumor metastasis. Exp Biol Med (Maywood) 233:779–791

    CAS  Google Scholar 

  • Sorensen MV, Matos JE, Sausbier M et al (2008) Aldosterone increases KCa1.1 (BK) channel-mediated colonic K+ secretion. J Physiol 586:4251–4264

    PubMed  PubMed Central  Google Scholar 

  • Stegen B, Butz L, Klumpp L et al (2015) Ca2+-activated IK K+ channel blockade radiosensitizes glioblastoma cells. Mol Cancer Res 13:1283–1295

    CAS  PubMed  Google Scholar 

  • Stegen B, Klumpp L, Misovic M et al (2016) K+ channel signaling in irradiated tumor cells. Eur Biophys J 45:585–598

    CAS  PubMed  Google Scholar 

  • Steinle M, Palme D, Misovic M et al (2011) Ionizing radiation induces migration of glioblastoma cells by activating BK K+ channels. Radiother Oncol 101:122–126

    CAS  PubMed  Google Scholar 

  • Steudel FA, Mohr CJ, Stegen B et al (2017) SK4 channels modulate Ca2+ signalling and cell cycle progression in murine breast cancer. Mol Oncol 11:1172–1188

    CAS  PubMed  PubMed Central  Google Scholar 

  • Strong MS, Vaughan CW, Kayne HL et al (1978) A randomized trial of preoperative radiotherapy in cancer of the oropharynx and hypopharynx. Am J Surg 136:494–500

    CAS  PubMed  Google Scholar 

  • Sui X, Geng JH, Li YH et al (2018) Calcium channel alpha2delta1 subunit (CACNA2D1) enhances radioresistance in cancer stem-like cells in non-small cell lung cancer cell lines. Cancer Manag Res 10:5009–5018

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tartier L, Gilchrist S, Burdak-Rothkamm S et al (2007) Cytoplasmic irradiation induces mitochondrial-dependent 53BP1 protein relocalization in irradiated and bystander cells. Cancer Res 67:5872–5879

    CAS  PubMed  PubMed Central  Google Scholar 

  • Terry S, Faouzi Zaarour R, Hassan Venkatesh G et al (2018) Role of hypoxic stress in regulating tumor immunogenicity, resistance and plasticity. Int J Mol Sci 19:3044

    Google Scholar 

  • Teshima K, Yamamoto A, Yamaoka K et al (2000) Involvement of calcium ion in elevation of mRNA for gamma-glutamylcysteine synthetase (gamma-GCS) induced by low-dose gamma-rays. Int J Radiat Biol 76:1631–1639

    CAS  PubMed  Google Scholar 

  • Thoday JM, Read J (1947) Effect of oxygen on the frequency of chromosome aberrations produced by X-rays. Nature 160:608

    CAS  PubMed  Google Scholar 

  • Todd DG, Mikkelsen RB (1994) Ionizing radiation induces a transient increase in cytosolic free [Ca2+] in human epithelial tumor cells. Cancer Res 54:5224–5230

    CAS  PubMed  Google Scholar 

  • Toulany M (2019) Targeting DNA double-strand break repair pathways to improve radiotherapy response. Genes (Basel) 10:25

    Google Scholar 

  • Trautmann F, Cojoc M, Kurth I et al (2014) CXCR4 as biomarker for radioresistant cancer stem cells. Int J Radiat Biol 90:687–699

    CAS  PubMed  Google Scholar 

  • Tyszka-Czochara M, Konieczny P, Majka M (2018) Recent advances in the role of AMP-activated protein kinase in metabolic reprogramming of metastatic cancer cells: targeting cellular bioenergetics and biosynthetic pathways for anti-tumor treatment. J Physiol Pharmacol:69

    Google Scholar 

  • Uysal-Onganer P, Djamgoz MB (2007) Epidermal growth factor potentiates in vitro metastatic behaviour of human prostate cancer PC-3M cells: involvement of voltage-gated sodium channel. Mol Cancer 6:76

    PubMed  PubMed Central  Google Scholar 

  • Valerie K, Povirk LF (2003) Regulation and mechanisms of mammalian double-strand break repair. Oncogene 22:5792–5812

    CAS  PubMed  Google Scholar 

  • Vercesi AE, Kowaltowski AJ, Grijalba MT et al (1997) The role of reactive oxygen species in mitochondrial permeability transition. Biosci Rep 17:43–52

    CAS  PubMed  Google Scholar 

  • Vilalta M, Rafat M, Graves EE (2016) Effects of radiation on metastasis and tumor cell migration. Cell Mol Life Sci 73:2999–3007

    CAS  PubMed  PubMed Central  Google Scholar 

  • Voehringer DW, Hirschberg DL, Xiao J et al (2000) Gene microarray identification of redox and mitochondrial elements that control resistance or sensitivity to apoptosis. Proc Natl Acad Sci U S A 97:2680–2685

    CAS  PubMed  PubMed Central  Google Scholar 

  • Voos P, Fuck S, Weipert F et al (2018) Ionizing radiation induces morphological changes and immunological modulation of Jurkat cells. Front Immunol 9:922

    PubMed  PubMed Central  Google Scholar 

  • Vullhorst D, Klocke R, Bartsch JW et al (1998) Expression of the potassium channel KV3.4 in mouse skeletal muscle parallels fiber type maturation and depends on excitation pattern. FEBS Lett 421:259–262

    CAS  PubMed  Google Scholar 

  • Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270

    CAS  PubMed  Google Scholar 

  • Weaver AK, Bomben VC, Sontheimer H (2006) Expression and function of calcium-activated potassium channels in human glioma cells. Glia 54:223–233

    PubMed  PubMed Central  Google Scholar 

  • Wojewodzka M, Walicka M, Sochanowicz B et al (1994) Calcium antagonist, TMB-8, prevents the induction of adaptive response by hydrogen peroxide or X-rays in human lymphocytes. Int J Radiat Biol 66:99–109

    CAS  PubMed  Google Scholar 

  • Wondergem R, Bartley JW (2009) Menthol increases human glioblastoma intracellular Ca2+, BK channel activity and cell migration. J Biomed Sci 16:90

    PubMed  PubMed Central  Google Scholar 

  • Wondergem R, Ecay TW, Mahieu F et al (2008) HGF/SF and menthol increase human glioblastoma cell calcium and migration. Biochem Biophys Res Commun 372:210–215

    CAS  PubMed  Google Scholar 

  • Wright EM, Ghezzi C, Loo DDF (2017) Novel and unexpected functions of SGLTs. Physiology (Bethesda) 32:435–443

    CAS  Google Scholar 

  • Xie H, Simon MC (2017) Oxygen availability and metabolic reprogramming in cancer. J Biol Chem 292:16825–16832

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Y, Miriyala S, Fang F et al (2015) Manganese superoxide dismutase deficiency triggers mitochondrial uncoupling and the Warburg effect. Oncogene 34:4229–4237

    PubMed  Google Scholar 

  • Yamamoto T (1936) Experimental study on effect of x-ray on metastasis of malignant tumor, especially in bones. Jpn J Obst Gynec 19:559–569

    Google Scholar 

  • Yamazaki H, Yoshida K, Yoshioka Y et al (2008) Impact of mitochondrial DNA on hypoxic radiation sensitivity in human fibroblast cells and osteosarcoma cell lines. Oncol Rep 19:1545–1549

    PubMed  Google Scholar 

  • Yang M, Brackenbury WJ (2013) Membrane potential and cancer progression. Front Physiol 4:185

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang M, Kozminski DJ, Wold LA et al (2012) Therapeutic potential for phenytoin: targeting Nav1.5 sodium channels to reduce migration and invasion in metastatic breast cancer. Breast Cancer Res Treat 134:603–615

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang B, Cao L, Liu J et al (2015) Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer. Cancer 121:1570–1580

    CAS  PubMed  Google Scholar 

  • Yildirim S, Altun S, Gumushan H et al (2012) Voltage-gated sodium channel activity promotes prostate cancer metastasis in vivo. Cancer Lett 323:58–61

    CAS  PubMed  Google Scholar 

  • Yom SS (2015) Accelerated repopulation as a cause of radiation treatment failure in non-small cell lung cancer: review of current data and future clinical strategies. Semin Radiat Oncol 25:93–99

    PubMed  Google Scholar 

  • Yoshida S (1997) Effects of X-irradiation on the calcium channel of the mouse oocyte. Life Sci 60:1377–1383

    CAS  PubMed  Google Scholar 

  • Zhang B, Davidson MM, Hei TK (2014) Mitochondria regulate DNA damage and genomic instability induced by high LET radiation. Life Sci Space Res 1:80–88

    Google Scholar 

  • Zhang J, Mao W, Dai Y et al (2019) Voltage-gated sodium channel Nav1.5 promotes proliferation, migration and invasion of oral squamous cell carcinoma. Acta Biochim Biophys Sin Shanghai 51:562–570

    CAS  PubMed  Google Scholar 

  • Zhang C, Ye L, Zhang Q et al (2020) The role of TRPV1 channels in atherosclerosis. Channels (Austin) 14:141–150

    Google Scholar 

  • Zhou H, Hong M, Chai Y et al (2009) Consequences of cytoplasmic irradiation: studies from microbeam. J Radiat Res 50(Suppl A):A59–A65

    CAS  PubMed  Google Scholar 

  • Zhou XB, Feng YX, Sun Q et al (2015) Nucleoside diphosphate kinase B-activated intermediate conductance potassium channels are critical for neointima formation in mouse carotid arteries. Arterioscler Thromb Vasc Biol 35:1852–1861

    CAS  PubMed  Google Scholar 

Download references

Acknowledgement

This project was supported by a grant of the German Cancer Aid (70112872/70113144).

Conflict of Interest

Both authors declare no competing interests.

Author information

Authors and Affiliations

  1. Department of Biology, Neurophysiology and Neurosensory Systems, Technische Universität Darmstadt, Darmstadt, Germany

    Bastian Roth

  2. Department of Radiation Oncology, University of Tübingen, Tübingen, Germany

    Stephan M. Huber

Authors
  1. Bastian Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephan M. Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephan M. Huber .

Editor information

Editors and Affiliations

  1. Medizinische Hochschule Hannover, Zentrum für Innere Medizin, Hannover, Germany

    Christian Stock

  2. Max-Planck-Institut für Multidisziplinäre Naturwissenschaften, Göttingen, Germany

    Luis A. Pardo

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Roth, B., Huber, S.M. (2020). Ion Transport and Radioresistance. In: Stock, C., Pardo, L.A. (eds) Targets of Cancer Diagnosis and Treatment. Reviews of Physiology, Biochemistry and Pharmacology, vol 183. Springer, Cham. https://doi.org/10.1007/112_2020_33

Download citation

Publish with us

Policies and ethics

Search

Navigation