{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:54:48Z","timestamp":1791312888135,"version":"4.3.1"},"reference-count":220,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T00:00:00Z","timestamp":1586217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics driven by a combination of poor vascular perfusion, regional hypoxia, and increased the flux of carbons through fermentative glycolysis. This leads to extracellular acidosis and intracellular alkalinization. Dysregulated pH dynamics influence cancer cell biology, from cell transformation and tumorigenesis to proliferation, local growth, invasion, and metastasis. Moreover, this dysregulated intracellular pH (pHi) drives a metabolic shift to increased aerobic glycolysis and reduced mitochondrial oxidative phosphorylation, referred to as the Warburg effect, or Warburg metabolism, which is a selective feature of cancer. This metabolic reprogramming confers a thermodynamic advantage on cancer cells and tissues by protecting them against oxidative stress, enhancing their resistance to hypoxia, and allowing a rapid conversion of nutrients into biomass to enable cell proliferation. Indeed, most cancers have increased glucose uptake and lactic acid production. Furthermore, cancer cells have very dysregulated electrolyte balances, and in the interaction of the pH dynamics with electrolyte, dynamics is less well known. In this review, we highlight the interconnected roles of dysregulated pH dynamics and electrolytes imbalance in cancer initiation, progression, adaptation, and in determining the programming and reprogramming of tumor cell metabolism.<\/jats:p>","DOI":"10.3390\/cancers12040898","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T05:59:47Z","timestamp":1586325587000},"page":"898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8656-6117","authenticated-orcid":false,"given":"Khalid O.","family":"Alfarouk","sequence":"first","affiliation":[{"name":"Alfarouk Biomedical Research LLC, Temple Terrace, FL 33617, USA"},{"name":"American Biosciences Inc., New York, NY 10913, USA"},{"name":"Hala Alfarouk Cancer Center, Khartoum 11123, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samrein B. M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Sharjah, P. O. Box 27272 Sharjah, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Oesphogastric and General Surgery, University Hospitals of Leicester, Leicester LE5 4PW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Elliott","sequence":"additional","affiliation":[{"name":"The Sallie A. Burdine Breast Foundation, Baton Rouge, LA 70806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muntaser E.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heyam S.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian C.","family":"Wales","sequence":"additional","affiliation":[{"name":"American Biosciences Inc., New York, NY 10913, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Nourwali","sequence":"additional","affiliation":[{"name":"College of Dentistry, Taibah University, Al-Madinah Al-Munwarah 42313, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed N.","family":"Aljarbou","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil H. H.","family":"Bashir","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari T. S.","family":"Alhoufie","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munwarah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad Saeed","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2011-9135","authenticated-orcid":false,"given":"Rosa A.","family":"Cardone","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 90126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Fais","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1725-757X","authenticated-orcid":false,"given":"Salvador","family":"Harguindey","sequence":"additional","affiliation":[{"name":"Institute for Clinical Biology and Metabolism, Postas 13, 01004 Vitoria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9757-5908","authenticated-orcid":false,"given":"Stephan J.","family":"Reshkin","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 90126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.18632\/oncoscience.109","article-title":"Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question","volume":"1","author":"Alfarouk","year":"2014","journal-title":"Oncoscience"},{"key":"ref_2","first-page":"1","article-title":"Tumor metabolism, cancer cell transporters, and microenvironmental resistance","volume":"6366","author":"Alfarouk","year":"2016","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1469-7793.1999.0633s.x","article-title":"Lactate transport in skeletal muscle\u2014Role and regulation of the monocarboxylate transporter","volume":"517","author":"Juel","year":"1999","journal-title":"J. Physiol."},{"key":"ref_4","unstructured":"Gladden, L.B. (2011). Lactate Transport and Exchange During Exercise. Comprehensive Physiology, John Wiley & Sons, Inc."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Korenchan, D.E., and Flavell, R.R. (2019). Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance. Cancers, 11.","DOI":"10.3390\/cancers11071026"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10555-018-09778-x","article-title":"What is pH regulation, and why do cancer cells need it?","volume":"38","author":"Swietach","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1053\/j.gastro.2019.05.004","article-title":"Regulation of pH by Carbonic Anhydrase 9 Mediates Survival of Pancreatic Cancer Cells With Activated KRAS in Response to Hypoxia","volume":"157","author":"McDonald","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.3390\/cancers3033002","article-title":"Evolution of tumor metabolism might reflect carcinogenesis as a reverse evolution process (dismantling of multicellularity)","volume":"3","author":"Alfarouk","year":"2011","journal-title":"Cancers"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1152\/physrev.00045.2006","article-title":"Regulation of Coronary Blood Flow During Exercise","volume":"88","author":"Duncker","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_10","first-page":"71","article-title":"Mechanisms for exercise training-induced increases in skeletal muscle blood flow capacity: Differences with interval sprint training versus aerobic endurance training","volume":"59","author":"Laughlin","year":"2008","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/japplphysiol.00789.2015","article-title":"Physical activity-induced remodeling of vasculature in skeletal muscle: Role in treatment of type 2 diabetes","volume":"120","author":"Laughlin","year":"2016","journal-title":"J. Appl. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ccr.2006.03.027","article-title":"Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members","volume":"9","author":"Certo","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1113\/eph8802513","article-title":"Response of Skeletal Muscle Mitochondria to Hypoxia","volume":"88","author":"Hoppeler","year":"2003","journal-title":"Exp. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/1871520616666161031143301","article-title":"The Warburg effect and the Hallmarks of Cancer","volume":"17","author":"Schwartz","year":"2017","journal-title":"Anticancer. Agents Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12465","DOI":"10.1002\/anie.201905965","article-title":"pH-Dependent Chloride Transport by Pseudopeptidic Cages for the Selective Killing of Cancer Cells in Acidic Microenvironments","volume":"58","author":"Tapia","year":"2019","journal-title":"Angew. Chemie Int. Ed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1152\/physiol.00005.2011","article-title":"Protons and Ca2+: Ionic allies in tumor progression?","volume":"26","author":"Glitsch","year":"2011","journal-title":"Physiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3389\/fphys.2013.00354","article-title":"Acidic tumor microenvironment and pH-sensing G protein-coupled receptors","volume":"4","author":"Justus","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fphys.2013.00370","article-title":"pH sensing and regulation in cancer","volume":"4","author":"Damaghi","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Maly, I.V., and Hofmann, W.A. (2018). Calcium and nuclear signaling in prostate cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041237"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3389\/fcell.2019.00154","article-title":"What Is Nuclear Factor Kappa B (NF-\u03baB) Doing in and to the Mitochondrion?","volume":"7","author":"Albensi","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1073\/pnas.81.15.4833","article-title":"A specific mutation abolishing Na+\/H+ antiport activity in hamster fibroblasts precludes growth at neutral and acidic pH","volume":"81","author":"Sardet","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","first-page":"4","article-title":"Increased H+ efflux is sufficient to induce dysplasia and necessary for viability with oncogene expression","volume":"4","author":"Choi","year":"2015","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.canlet.2011.11.023","article-title":"The Na+\/H+ exchanger NHE1, but not the Na+, cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2","volume":"317","author":"Lauritzen","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1002\/ijc.27782","article-title":"Contribution of Na+,HCO3\u2212-cotransport to cellular pH control in human breast cancer: A role for the breast cancer susceptibility locus NBCn1 (SLC4A7)","volume":"132","author":"Boedtkjer","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1158\/0008-5472.CAN-15-1862","article-title":"Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth","volume":"76","author":"McIntyre","year":"2016","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"439","DOI":"10.18433\/J34608","article-title":"Use of proton pump inhibitors as adjunct treatment for triple-negative breast cancers. An introductory study","volume":"17","author":"Goh","year":"2014","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1139\/o02-151","article-title":"Structure and function of the NHE1 isoform of the Na+\/H+ exchanger","volume":"80","author":"Slepkov","year":"2002","journal-title":"Biochem. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1073\/pnas.93.2.654","article-title":"Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification","volume":"93","author":"Gottlieb","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/35014006","article-title":"Changes in intramitochondrial and cytosolic pH: Early events that modulate caspase activation during apoptosis","volume":"2","author":"Matsuyama","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/sj.cdd.4401466","article-title":"Alterations of intracellular pH homeostasis in apoptosis: Origins and roles","volume":"11","author":"Huc","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9244","DOI":"10.1074\/jbc.275.13.9244","article-title":"Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis","volume":"275","author":"Liu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1100\/tsw.2001.159","article-title":"Activation of the JNK\/SAPK and P38 Mitogen-Activated Protein Kinase Signaling Pathways Sensitize Tumor Cells to Cisplatin-Induced Apoptosis","volume":"1","author":"Mansouri","year":"2001","journal-title":"Sci. World J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6235","DOI":"10.1074\/jbc.270.11.6235","article-title":"Intracellular alkalinization suppresses lovastatin-induced apoptosis in HL-60 cells through the inactivation of a pH-dependent endonuclease","volume":"270","author":"Mollinedo","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_34","first-page":"3930","article-title":"Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice","volume":"118","author":"Sonveaux","year":"2008","journal-title":"J. Clin. Invest."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/mc.21863","article-title":"Metabolic symbiosis in cancer: Refocusing the Warburg lens","volume":"52","author":"Nakajima","year":"2013","journal-title":"Mol. Carcinog."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.bbabio.2010.10.012","article-title":"Choosing between glycolysis and oxidative phosphorylation: A tumor\u2019s dilemma?","volume":"1807","author":"Jose","year":"2011","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.biocel.2010.05.003","article-title":"Waves of gene regulation suppress and then restore oxidative phosphorylation in cancer cells","volume":"43","author":"Bellance","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.4161\/cc.8.23.10238","article-title":"The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma","volume":"8","author":"Pavlides","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/eva.12015","article-title":"Riparian ecosystems in human cancers","volume":"6","author":"Alfarouk","year":"2013","journal-title":"Evol. Appl."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lloyd, M.C., Alfarouk, K.O., Verduzco, D., Bui, M.M., Gillies, R.J., Ibrahim, M.E., Brown, J.S., and Gatenby, R.A. (2014). Vascular measurements correlate with estrogen receptor status. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-279"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"408","DOI":"10.3390\/cancers3010408","article-title":"Tumor acidity as evolutionary spite","volume":"3","author":"Alfarouk","year":"2011","journal-title":"Cancers"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12935-015-0221-1","article-title":"Resistance to cancer chemotherapy: Failure in drug response from ADME to P-gp","volume":"15","author":"Alfarouk","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ccr.2006.04.023","article-title":"Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance","volume":"9","author":"Fantin","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.cmet.2014.03.003","article-title":"Targeting Lactate Dehydrogenase-A Inhibits Tumorigenesis and Tumor Progression in Mouse Models of Lung Cancer and Impacts Tumor-Initiating Cells","volume":"19","author":"Xie","year":"2014","journal-title":"Cell Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.ccr.2013.02.005","article-title":"Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer","volume":"23","author":"Zhao","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#","article-title":"Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase","volume":"43","author":"Read","year":"2001","journal-title":"Proteins"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.molcel.2013.07.012","article-title":"Protons as Second Messenger Regulators of G Protein Signaling","volume":"51","author":"Isom","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S0006-291X(05)80213-X","article-title":"Regulation of muscle phosphofructokinase by physiological concentrations of bisphosphorylated hexoses: Effect of alkalinization","volume":"172","author":"Carreras","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1002\/jcb.24039","article-title":"Phosphofructokinase type 1 kinetics, isoform expression, and gene polymorphisms in cancer cells","volume":"113","author":"Quezada","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nature14405","article-title":"Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations","volume":"523","author":"Webb","year":"2015","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s10147-017-1156-4","article-title":"Targeting metabolic reprogramming in KRAS-driven cancers","volume":"22","author":"Kawada","year":"2017","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrm2438","article-title":"Ras oncogenes: Split personalities","volume":"9","author":"Karnoub","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"807","DOI":"10.18632\/oncoscience.253","article-title":"Synthetic lethality in KRas-driven cancer cells created by glutamine deprivation","volume":"2","author":"Mukhopadhyay","year":"2015","journal-title":"Oncoscience"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1126\/science.1174229","article-title":"Glucose Deprivation Contributes to the Development of KRAS Pathway Mutations in Tumor Cells","volume":"325","author":"Yun","year":"2009","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1074\/mcp.M116.058925","article-title":"Oncogenic KRAS and BRAF Drive Metabolic Reprogramming in Colorectal Cancer","volume":"15","author":"Hutton","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1126\/science.aaa5004","article-title":"Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH","volume":"350","author":"Yun","year":"2015","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tai, C.-J., Wang, W.-C., Wang, C.-K., Wu, C.-H., Yang, M.-D., Chang, Y.-J., Jian, J.-Y., and Tai, C.-J. (2013). Fermented Wheat Germ Extract Induced Cell Death and Enhanced Cytotoxicity of Cisplatin and 5-Fluorouracil on Human Hepatocellular Carcinoma Cells. Evidence-Based Complement. Altern. Med. Suppl., 2013.","DOI":"10.1155\/2013\/121725"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"46408","DOI":"10.1074\/jbc.M206150200","article-title":"Fermented Wheat Germ Extract Inhibits Glycolysis\/Pentose Cycle Enzymes and Induces Apoptosis through Poly(ADP-ribose) Polymerase Activation in Jurkat T-cell Leukemia Tumor Cells","volume":"277","author":"Boros","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.semcancer.2017.01.005","article-title":"Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH","volume":"43","author":"Schwartz","year":"2017","journal-title":"Semin. Cancer Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/13543776.2020.1704733","article-title":"Drug repurposing for anticancer therapies. A lesson from proton pump inhibitors","volume":"30","author":"Spugnini","year":"2020","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/tbj.13519","article-title":"Proton pump inhibitors reduce breast cancer risk in gastric ulcer patients: A population-based cohort study","volume":"26","author":"Ding","year":"2019","journal-title":"Breast J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/jcph.1329","article-title":"Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population-Based Study","volume":"59","author":"Chen","year":"2019","journal-title":"J. Clin. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3550","DOI":"10.1038\/ncomms4550","article-title":"Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival","volume":"5","author":"Khacho","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5507","DOI":"10.1158\/0008-5472.CAN-14-0705","article-title":"The SIRT1\/HIF2\u03b1 Axis Drives Reductive Glutamine Metabolism under Chronic Acidosis and Alters Tumor Response to Therapy","volume":"74","author":"Corbet","year":"2014","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.1158\/0008-5472.CAN-15-2630","article-title":"Acidosis Acts through HSP90 in a PHD\/VHL-Independent Manner to Promote HIF Function and Stem Cell Maintenance in Glioma","volume":"76","author":"Filatova","year":"2016","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1016\/j.celrep.2017.02.006","article-title":"Extracellular Acidic pH Activates the Sterol Regulatory Element-Binding Protein 2 to Promote Tumor Progression","volume":"18","author":"Kondo","year":"2017","journal-title":"Cell Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrc3579","article-title":"Disrupting proton dynamics and energy metabolism for cancer therapy","volume":"13","author":"Parks","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1002\/jcp.24346","article-title":"Hypoxia promotes tumor cell survival in acidic conditions by preserving ATP levels","volume":"228","author":"Parks","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1158\/0008-5472.CAN-11-2474","article-title":"Regulation of Monocarboxylate Transporter MCT1 Expression by p53 Mediates Inward and Outward Lactate Fluxes in Tumors","volume":"72","author":"Boidot","year":"2011","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1158\/0008-5472.CAN-10-2828","article-title":"Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-\u03baB\/IL-8 pathway that drives tumor angiogenesis","volume":"71","author":"Boidot","year":"2011","journal-title":"Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.celrep.2016.04.028","article-title":"Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy","volume":"15","author":"Pisarsky","year":"2016","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/ncb1144","article-title":"HIF activation by pH-dependent nucleolar sequestration of VHL","volume":"6","author":"Mekhail","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/cdd.2010.150","article-title":"Acidic stress promotes a glioma stem cell phenotype","volume":"18","author":"Hjelmeland","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1158\/0008-5472.CAN-11-2076","article-title":"Functional Interaction between Responses to Lactic Acidosis and Hypoxia Regulates Genomic Transcriptional Outputs","volume":"72","author":"Tang","year":"2012","journal-title":"Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chen, J.L.-Y., Lucas, J.E., Schroeder, T., Mori, S., Wu, J., Nevins, J., Dewhirst, M., West, M., and Chi, J.-T. (2008). The Genomic Analysis of Lactic Acidosis and Acidosis Response in Human Cancers. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000293"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1126\/science.1169956","article-title":"Regulation of Hypoxia-Inducible Factor 2 Signaling by the Stress-Responsive Deacetylase Sirtuin 1","volume":"324","author":"Dioum","year":"2009","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Schug, Z.T., Peck, B., Jones, D.T., Zhang, Q., Grosskurth, S., Alam, I.S., Goodwin, L.M., Smethurst, E., Mason, S., and Blyth, K. (2015). Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell.","DOI":"10.1186\/2049-3002-2-S1-O9"},{"key":"ref_78","first-page":"57","article-title":"Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress Cancer & Metabolism","volume":"27","author":"LaMonte","year":"2013","journal-title":"Cancer Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1093\/brain\/awf257","article-title":"Hypoxia-induced vascular endothelial growth factor expression causes vascular leakage in the brain","volume":"125","author":"Schoch","year":"2002","journal-title":"Brain"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1038\/sj.onc.1204500","article-title":"Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells","volume":"20","author":"Shi","year":"2001","journal-title":"Oncogene"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1215\/15228517-2008-106","article-title":"Lactate promotes glioma migration by TGF-beta2-dependent regulation of matrix metalloproteinase-2","volume":"11","author":"Baumann","year":"2009","journal-title":"Neuro. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1158\/1538-7445.AM2012-2467","article-title":"Abstract 2467: Acidic pericellular pH increases contribution of cathepsin B to invasiveness of a human breast carcinoma cell line","volume":"72","author":"Rothberg","year":"2012","journal-title":"Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6921","DOI":"10.1158\/0008-5472.CAN-11-1457","article-title":"Lactate: A metabolic key player in cancer","volume":"71","author":"Hirschhaeuser","year":"2011","journal-title":"Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Singh, S., Lomelino, C., Mboge, M., Frost, S., and McKenna, R. (2018). Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site. Molecules, 23.","DOI":"10.3390\/molecules23051045"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Supuran, C.T. (2018). Carbonic Anhydrases and Metabolism. Metabolites, 8.","DOI":"10.3390\/metabo8020025"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1365-2796.1990.tb00247.x","article-title":"The effect of carbonic anhydrase inhibition on calcium and bone homeostasis in healthy postmenopausal women","volume":"228","author":"Gram","year":"1990","journal-title":"J. Intern. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5299","DOI":"10.1113\/JP271378","article-title":"Essential role of carbonic anhydrase XII in secretory gland fluid and HCO3\u2212 secretion revealed by disease causing human mutation","volume":"593","author":"Hong","year":"2015","journal-title":"J. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1016\/j.ejca.2005.09.011","article-title":"The role of carbonic anhydrase IX overexpression in kidney cancer","volume":"41","author":"Dorai","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"125","DOI":"10.4143\/crt.2014.243","article-title":"The Expression of Carbonic Anhydrase (CA) IX\/XII and Lymph Node Metastasis in Early Breast Cancer","volume":"48","author":"Eom","year":"2016","journal-title":"Cancer Res. Treat."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Mboge, M.Y., Mahon, B.P., McKenna, R., and Frost, S.C. (2018). Carbonic Anhydrases: Role in pH Control and Cancer. Metabolites, 8.","DOI":"10.3390\/metabo8010019"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1080\/14756366.2018.1538980","article-title":"Prostate cancer cells and exosomes in acidic condition show increased carbonic anhydrase IX expression and activity","volume":"34","author":"Logozzi","year":"2019","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.ejcb.2010.03.004","article-title":"Carbonic anhydrase XII promotes invasion and migration ability of MDA-MB-231 breast cancer cells through the p38 MAPK signaling pathway","volume":"89","author":"Hsieh","year":"2010","journal-title":"Eur. J. Cell Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3233\/JAD-2010-100384","article-title":"Plasma Carbonic Anhydrase II protein is Elevated in Alzheimer\u2019s Disease","volume":"21","author":"Jang","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1093\/carcin\/bgx148","article-title":"Carbonic anhydrase 2 inhibits epithelial\u2013mesenchymal transition and metastasis in hepatocellular carcinoma","volume":"39","author":"Zhang","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"790","DOI":"10.2174\/187152008785914798","article-title":"Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression","volume":"8","author":"Cosse","year":"2008","journal-title":"Anticancer. Agents Med. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1021\/mp200292c","article-title":"Drug resistance and cellular adaptation to tumor acidic pH microenvironment","volume":"8","author":"Wojtkowiak","year":"2011","journal-title":"Mol. Pharm."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Ward, C., Meehan, J., Gray, M., Kunkler, I., Langdon, S., and Argyle, D. (2018). Carbonic Anhydrase IX (CAIX), Cancer, and Radiation Responsiveness. Metabolites, 8.","DOI":"10.3390\/metabo8010013"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"9023","DOI":"10.1007\/s13277-016-4785-8","article-title":"Inhibition of carbonic anhydrase potentiates bevacizumab treatment in cholangiocarcinoma","volume":"37","author":"Vaeteewoottacharn","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"36666","DOI":"10.18632\/oncotarget.9134","article-title":"Targeting carbonic anhydrase IX improves the anti-cancer efficacy of mTOR inhibitors","volume":"7","author":"Faes","year":"2016","journal-title":"Oncotarget"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s00428-014-1709-0","article-title":"Expression of carbonic anhydrase 9 is a novel prognostic marker in resectable hepatocellular carcinoma","volume":"466","author":"Kang","year":"2015","journal-title":"Virchows Arch."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.2147\/CMAR.S163747","article-title":"Comparison of NSAIDs activity in COX-2 expressing and non-expressing 2D and 3D pancreatic cancer cell cultures","volume":"10","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.orthres.2004.03.002","article-title":"Hypoxia induces HIF-1\u03b1 and VEGF expression in chondrosarcoma cells and chondrocytes","volume":"22","author":"Lin","year":"2004","journal-title":"J. Orthop. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"14608","DOI":"10.1073\/pnas.97.26.14608","article-title":"Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood","volume":"97","author":"Chang","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1073\/pnas.98.2.398","article-title":"Can mosaic tumor vessels facilitate molecular diagnosis of cancer?","volume":"98","author":"Folkman","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5740","DOI":"10.1158\/0008-5472.CAN-04-4552","article-title":"Mosaic tumor vessels: Cellular basis and ultrastructure of focal regions lacking endothelial cell markers","volume":"65","author":"Capen","year":"2005","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"11368","DOI":"10.1074\/jbc.M108347200","article-title":"Acidic extracellular pH induces vascular endothelial growth factor (VEGF) in human glioblastoma cells via ERK1\/2 MAPK signaling pathway: Mechanism of low pH-induced VEGF","volume":"277","author":"Xu","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_108","first-page":"5381","article-title":"Significance of blood vessel leakiness in cancer","volume":"62","author":"McDonald","year":"2002","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/sj.bjc.6604929","article-title":"Why are tumour blood vessels abnormal and why is it important to know?","volume":"100","author":"Nagy","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrd1381","article-title":"Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer","volume":"3","author":"Ferrara","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.bbrc.2005.05.132","article-title":"Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy","volume":"333","author":"Ferrara","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1096\/fj.00-0029com","article-title":"Na+\/H+ exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes","volume":"14","author":"Reshkin","year":"2000","journal-title":"FASEB J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1152\/advan.00045.2004","article-title":"Regulation of intracellular pH","volume":"28","author":"Boron","year":"2004","journal-title":"Adv. Physiol. Educ."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"20130100","DOI":"10.1098\/rstb.2013.0100","article-title":"Role of pHi, and proton transporters in oncogene-driven neoplastic transformation","volume":"369","author":"Reshkin","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1016\/j.bbamcr.2016.02.018","article-title":"Na+\/H+ antiporter (NHE1) and lactate\/H+ symporters (MCTs) in pH homeostasis and cancer metabolism","volume":"1863","author":"Counillon","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrc1713","article-title":"The role of disturbed pH dynamics and the Na+\/H+ exchanger in metastasis","volume":"5","author":"Cardone","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1093\/carcin\/bgu089","article-title":"Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H+ extrusion, cell migration and survival","volume":"35","author":"Cong","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s12943-015-0357-6","article-title":"ZEB1 transcriptionally regulated carbonic anhydrase 9 mediates the chemoresistance of tongue cancer via maintaining intracellular pH","volume":"14","author":"Zheng","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1158\/0008-5472.CAN-15-0857","article-title":"Carbonic Anhydrase Activity Monitored In Vivo by Hyperpolarized 13C-Magnetic Resonance Spectroscopy Demonstrates Its Importance for pH Regulation in Tumors","volume":"75","author":"Gallagher","year":"2015","journal-title":"Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1002\/jcp.24930","article-title":"The Na+\/HCO3\u2212 Co-Transporter SLC4A4 Plays a Role in Growth and Migration of Colon and Breast Cancer Cells","volume":"230","author":"Parks","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1038\/onc.2015.273","article-title":"Disrupting Na+, HCO3\u2212-cotransporter NBCn1 (Slc4a7) delays murine breast cancer development","volume":"35","author":"Lee","year":"2016","journal-title":"Oncogene"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3389\/fphys.2014.00130","article-title":"Regulation and roles of bicarbonate transporters in cancer","volume":"5","author":"Gorbatenko","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Cardone, R., Alfarouk, K., Elliott, R., Alqahtani, S., Ahmed, S., Aljarbou, A., Greco, M., Cannone, S., and Reshkin, S. (2019). The Role of Sodium Hydrogen Exchanger 1 in Dysregulation of Proton Dynamics and Reprogramming of Cancer Metabolism as a Sequela. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153694"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1242\/jcs.195297","article-title":"Cancer cell behaviors mediated by dysregulated pH dynamics at a glance","volume":"130","author":"White","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nrc3110","article-title":"Dysregulated pH: A perfect storm for cancer progression","volume":"11","author":"Webb","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Harguindey, S., Orozco, J.P., Alfarouk, K.O., and Devesa, J. (2019). Hydrogen ion dynamics of cancer and a new molecular, biochemical and metabolic approach to the etiopathogenesis and treatment of brain malignancies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174278"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Harguindey, S., Alfarouk, K., Orozco, J.P., Hardonniere, K., Stanciu, D., Fais, S., and Devesa, J. (2020). A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031110"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.semcancer.2017.02.008","article-title":"The new pH-centric anticancer paradigm in Oncology and Medicine; SCB, 2017","volume":"43","author":"Harguindey","year":"2017","journal-title":"Semin. Cancer Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"115","DOI":"10.15171\/bi.2017.15","article-title":"Molecular machineries of pH dysregulation in tumor microenvironment: Potential targets for cancer therapy","volume":"7","author":"Asgharzadeh","year":"2017","journal-title":"BioImpacts"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1038\/s41467-018-05261-x","article-title":"Systems analysis of intracellular pH vulnerabilities for cancer therapy","volume":"9","author":"Persi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3389\/fphar.2015.00152","article-title":"Voltage-gated sodium channels and cancer: Is excitability their primary role?","volume":"6","author":"Roger","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"20130105","DOI":"10.1098\/rstb.2013.0105","article-title":"Regulation of voltage-gated sodium channel expression in cancer: Hormones, growth factors and auto-regulation","volume":"369","author":"Fraser","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1002\/ijc.30381","article-title":"Voltage-gated sodium channel Nav1.7 promotes gastric cancer progression through MACC1-mediated upregulation of NHE1","volume":"139","author":"Xia","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1387\/ijdb.150171wb","article-title":"Dual roles of voltage-gated sodium channels in development and cancer","volume":"59","author":"Patel","year":"2015","journal-title":"Int. J. Dev. Biol."},{"key":"ref_135","first-page":"571","article-title":"An Emerging Role for Voltage-Gated Na+ Channels in Cellular Migration: Regulation of Central Nervous System Development and Potentiation of Invasive Cancers","volume":"14","author":"Brackenbury","year":"2008","journal-title":"Neurosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ejphar.2009.08.040","article-title":"Molecular pharmacology of voltage-gated sodium channel expression in metastatic disease: Clinical potential of neonatal Nav1.5 in breast cancer","volume":"625","author":"Onkal","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"297","DOI":"10.12688\/f1000research.6789.1","article-title":"Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed drugs","volume":"4","author":"Koltai","year":"2015","journal-title":"F1000Research"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3892\/ijo.2015.3239","article-title":"Blockade of voltage-gated sodium channels inhibits invasion of endocrine-resistant breast cancer cells","volume":"48","author":"Mohammed","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1353\/pbm.1976.0071","article-title":"Tetrodotoxin: From poison to powerful tool","volume":"19","author":"Blankenship","year":"1976","journal-title":"Perspect. Biol. Med."},{"key":"ref_140","first-page":"232","article-title":"Evolutionary history of a complex adaptation: Tetrodotoxin resistance in salamanders","volume":"69","author":"Hanifin","year":"2015","journal-title":"Evolution (N. Y.)"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1085\/jgp.47.5.965","article-title":"Tetrodotoxin Blockage of Sodium Conductance Increase in Lobster Giant Axons","volume":"47","author":"Narahashi","year":"1964","journal-title":"J. Gen. Physiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jpainsymman.2007.05.011","article-title":"Tetrodotoxin for Moderate to Severe Cancer Pain: A Randomized, Double Blind, Parallel Design Multicenter Study","volume":"35","author":"Hagen","year":"2008","journal-title":"J. Pain Symptom Manag."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.3747\/co.v18i3.732","article-title":"A multicentre open-label safety and efficacy study of tetrodotoxin for cancer pain","volume":"18","author":"Hagen","year":"2011","journal-title":"Curr. Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2183\/pjab.84.147","article-title":"Tetrodotoxin: A brief history","volume":"84","author":"Narahashi","year":"2008","journal-title":"Proc. Jpn. Acad. Ser. B. Phys. Biol. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10549-012-2102-9","article-title":"Therapeutic potential for phenytoin: Targeting Nav1.5 sodium channels to reduce migration and invasion in metastatic breast cancer","volume":"134","author":"Yang","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_146","first-page":"662","article-title":"Selective killing effect of oxytetracycline, propafenone and metamizole on A549 or Hela cells","volume":"25","author":"Shao","year":"2013","journal-title":"Chin. J. Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ejps.2006.10.002","article-title":"Na+\/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells","volume":"30","author":"Friedlander","year":"2007","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"188","DOI":"10.2174\/187152907781745288","article-title":"Na+\/Ca2+ Exchange Inhibitors: A New Class of Calcium Regulators","volume":"7","author":"Iwamoto","year":"2008","journal-title":"Cardiovasc. Hematol. Disord. Targets"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.bcp.2019.02.032","article-title":"Na+\/Ca2+ exchangers: Unexploited opportunities for cancer therapy?","volume":"163","author":"Rodrigues","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Liskova, V., Hudecova, S., Lencesova, L., Iuliano, F., Sirova, M., Ondrias, K., Pastorekova, S., and Krizanova, O. (2019). Type 1 Sodium Calcium Exchanger Forms a Complex with Carbonic Anhydrase IX and Via Reverse Mode Activity Contributes to pH Control in Hypoxic Tumors. Cancers, 11.","DOI":"10.3390\/cancers11081139"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1186\/1479-5876-11-282","article-title":"Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs-an integral molecular\/biochemical\/metabolic\/clinical approach after one hundred years of cancer research","volume":"11","author":"Harguindey","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.semcancer.2017.02.003","article-title":"Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases","volume":"43","author":"Harguindey","year":"2017","journal-title":"Semin. Cancer Biol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"91","DOI":"10.4155\/ppa.12.3","article-title":"Na+\/K+-ATPase and cancer","volume":"1","author":"Mijatovic","year":"2012","journal-title":"Pharm. Pat. Anal."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"988","DOI":"10.2174\/1389450115666140908125025","article-title":"Na+\/K+ ATPase Inhibitors in Cancer","volume":"15","author":"Alevizopoulos","year":"2018","journal-title":"Curr. Drug Targets"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Khajah, M.A., Mathew, P.M., and Luqmani, Y.A. (2018). Na+\/K+ ATPase activity promotes invasion of endocrine resistant breast cancer cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193779"},{"key":"ref_156","first-page":"65","article-title":"Potassium, sodium, and cancer: A review","volume":"15","author":"Jansson","year":"1996","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nature19364","article-title":"Ionic immune suppression within the tumour microenvironment limits T cell effector function","volume":"537","author":"Eil","year":"2016","journal-title":"Nature"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2174\/1574892811308010085","article-title":"Na+-H+ exchanger, pH regulation and cancer","volume":"8","author":"Reshkin","year":"2013","journal-title":"Recent Pat. Anticancer. Drug Discov."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1016\/j.febslet.2006.03.062","article-title":"Potassium channels as tumour markers","volume":"580","author":"Alves","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00232-005-0781-4","article-title":"Ion Channels and Cancer","volume":"205","author":"Kunzelmann","year":"2005","journal-title":"J. Membr. Biol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00232-005-0776-1","article-title":"Role of Voltage-gated Potassium Channels in Cancer","volume":"205","author":"Pardo","year":"2005","journal-title":"J. Membr. Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1152\/physiol.00011.2004","article-title":"Voltage-Gated Potassium Channels in Cell Proliferation","volume":"19","author":"Pardo","year":"2004","journal-title":"Physiology"},{"key":"ref_163","first-page":"261","article-title":"Blockage of voltage-gated K+ channels inhibits adhesion and proliferation of hepatocarcinoma cells","volume":"11","author":"Zhou","year":"2003","journal-title":"Int. J. Mol. Med."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Choi, S.Y., Kim, H.-R., Ryu, P.D., and Lee, S.Y. (2017). Regulation of voltage-gated potassium channels attenuates resistance of side-population cells to gefitinib in the human lung cancer cell line NCI-H460. BMC Pharmacol. Toxicol., 18.","DOI":"10.1186\/s40360-017-0118-9"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2174\/187152011795347513","article-title":"Astemizole: An old anti-histamine as a new promising anti-cancer drug","volume":"11","author":"Camacho","year":"2011","journal-title":"Anticancer. Agents Med. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1083\/jcb.201404136","article-title":"Targeting potassium channels in cancer","volume":"206","author":"Huang","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_167","first-page":"3345","article-title":"Tumor suppressive role of rottlerin in cancer therapy","volume":"10","author":"Ma","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Asensio-L\u00f3pez, M.C., Soler, F., Pascual-Figal, D., Fern\u00e1ndez-Belda, F., and Lax, A. (2017). Doxorubicin-induced oxidative stress: The protective effect of nicorandil on HL-1 cardiomyocytes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172803"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"172542","DOI":"10.1016\/j.ejphar.2019.172542","article-title":"Nicorandil prevents doxorubicin-induced human umbilical vein endothelial cell apoptosis","volume":"859","author":"Chen","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_170","first-page":"3691","article-title":"Fluoxetine-induced apoptosis in hepatocellular carcinoma cells","volume":"33","author":"Mun","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Chen, W.-T., Hsu, F.-T., Liu, Y.-C., Chen, C.-H., Hsu, L.-C., and Lin, S.-S. (2019). Fluoxetine Induces Apoptosis through Extrinsic\/Intrinsic Pathways and Inhibits ERK\/NF-\u03baB-Modulated Anti-Apoptotic and Invasive Potential in Hepatocellular Carcinoma Cells In Vitro. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030757"},{"key":"ref_172","first-page":"10521","article-title":"Fluoxetine enhances cellular chemosensitivity to Cisplatin in cervical cancer","volume":"10","author":"Liu","year":"2017","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.apsb.2016.11.001","article-title":"Targeting calcium signaling in cancer therapy","volume":"7","author":"Cui","year":"2017","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0143-4160(98)90116-6","article-title":"The role of calcium in apoptosis","volume":"23","author":"Nicotera","year":"1998","journal-title":"Cell Calcium"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"6407","DOI":"10.1038\/onc.2008.308","article-title":"Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis","volume":"27","author":"Pinton","year":"2008","journal-title":"Oncogene"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/sj.cdd.4401950","article-title":"Mechanisms of cytochrome c release from mitochondria","volume":"13","author":"Garrido","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.neuint.2017.10.003","article-title":"Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria","volume":"117","author":"Andreyev","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0014-4827(71)90225-4","article-title":"Cyclic AMP-mediated stimulation by calcium of thymocyte proliferation","volume":"69","author":"Macmanus","year":"1971","journal-title":"Exp. Cell Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1016\/j.cellsig.2015.08.006","article-title":"Calcium signaling and cell proliferation","volume":"27","author":"Pinto","year":"2015","journal-title":"Cell. Signal."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/bies.950170605","article-title":"Calcium signalling and cell proliferation","volume":"17","author":"Berridge","year":"1995","journal-title":"BioEssays"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1582-4934.2004.tb00271.x","article-title":"Intracellular calcium signals and control of cell proliferation: How many mechanisms?","volume":"8","author":"Munaron","year":"2004","journal-title":"J. Cell. Mol. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/cm.20367","article-title":"The effects of extracellular calcium on motility, pseudopod and uropod formation, chemotaxis, and the cortical localization of myosin II in Dictyostelium discoideum","volume":"66","author":"Lusche","year":"2009","journal-title":"Cell Motil. Cytoskeleton"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ceb.2011.12.002","article-title":"Calcium gradients underlying cell migration","volume":"24","author":"Wei","year":"2012","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_184","first-page":"1","article-title":"Ca2+ signaling in cytoskeletal reorganization, cell migration, and cancer metastasis","volume":"2015","author":"Tsai","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1016\/j.bbamem.2015.03.034","article-title":"Targeting ion channels for cancer therapy by repurposing the approved drugs","volume":"1848","author":"Kale","year":"2015","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/glia.20063","article-title":"Expression of T-type calcium channel splice variants in human glioma","volume":"48","author":"Latour","year":"2004","journal-title":"Glia"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"10162","DOI":"10.1074\/jbc.M707159200","article-title":"CaV3.2 T-type calcium channels are involved in calcium-dependent secretion of neuroendocrine prostate cancer cells","volume":"283","author":"Bidaux","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_188","first-page":"267","article-title":"T-type voltage-activated calcium channel Ca v3.1, but not Ca v3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells","volume":"41","author":"Ohkubo","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s00424-014-1444-z","article-title":"T-type calcium channels blockers as new tools in cancer therapies","volume":"466","author":"Dziegielewska","year":"2014","journal-title":"Pflugers Arch. Eur. J. Physiol."},{"key":"ref_190","first-page":"49","article-title":"Plasma membrane Ca2+ ATPase isoform 1 down-regulated in human oral cancer","volume":"15","author":"Saito","year":"2006","journal-title":"Oncol. Rep."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.bbrc.2007.02.050","article-title":"Plasma membrane Ca2+-ATPase expression during colon cancer cell line differentiation","volume":"355","author":"Aung","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.bbamcr.2015.11.016","article-title":"Calcium-ATPases: Gene disorders and dysregulation in cancer","volume":"1863","author":"Dang","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ejphar.2005.04.010","article-title":"Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue","volume":"515","author":"Collado","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/j.1365-2559.2010.03683.x","article-title":"Expression of transient receptor potential vanilloid-1 (TRPV1) in urothelial cancers of human bladder: Relation to clinicopathological and molecular parameters","volume":"57","author":"Kalogris","year":"2010","journal-title":"Histopathology"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/1097-0142(19950201)75:3<815::AID-CNCR2820750311>3.0.CO;2-R","article-title":"A phase III randomized study of oral verapamil as a chemosensitizer to reverse drug resistance in patients with refractory myeloma. A southwest oncology group study","volume":"75","author":"Dalton","year":"1995","journal-title":"Cancer"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1089\/adt.2015.29014.ajkdrrr","article-title":"Repurposing and rescuing of mibefradil, an antihypertensive, for cancer: A case study","volume":"13","author":"Krouse","year":"2015","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1016\/j.febslet.2010.01.037","article-title":"Chloride channels of intracellular membranes","volume":"584","author":"Edwards","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Liu, B., Billington, C.K., Henry, A.P., Bhaker, S.K., Kheirallah, A.K., Swan, C., and Hall, I.P. (2018). Chloride intracellular channel 1 (CLIC1) contributes to modulation of cyclic AMP-activated whole-cell chloride currents in human bronchial epithelial cells. Physiol. Rep., 6.","DOI":"10.14814\/phy2.13508"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"26003","DOI":"10.1074\/jbc.M203666200","article-title":"Recombinant CLIC1 (NCC27) Assembles in Lipid Bilayers via a pH-dependent Two-state Process to Form Chloride Ion Channels with Identical Characteristics to Those Observed in Chinese Hamster Ovary Cells Expressing CLIC1","volume":"277","author":"Warton","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1016\/j.febslet.2010.02.073","article-title":"Chloride intracellular channel 1 (CLIC1): Sensor and effector during oxidative stress","volume":"584","author":"Averaimo","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"12575","DOI":"10.1074\/jbc.272.19.12575","article-title":"Molecular cloning and expression of a chloride ion channel of cell nuclei","volume":"272","author":"Valenzuela","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1091\/mbc.11.5.1509","article-title":"Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that associates with the actin cytoskeleton of placental microvilli","volume":"11","author":"Berryman","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"44993","DOI":"10.1074\/jbc.M107804200","article-title":"Crystal Structure of a Soluble Form of the Intracellular Chloride Ion Channel CLIC1 (NCC27) at 1.4-\u00c5 Resolution","volume":"276","author":"Harrop","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Xu, Y., Zhu, J., Hu, X., Wang, C., Lu, D., Gong, C., Yang, J., and Zong, L. (2016). CLIC1 Inhibition Attenuates Vascular Inflammation, Oxidative Stress, and Endothelial Injury. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166790"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"31413","DOI":"10.18632\/oncotarget.5105","article-title":"Extracellular vesicle-mediated transfer of CLIC1 protein is a novel mechanism for the regulation of glioblastoma growth","volume":"6","author":"Setti","year":"2015","journal-title":"Oncotarget"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s12032-015-0616-9","article-title":"Chloride intracellular channel 1 (CLIC1) is activated and functions as an oncogene in pancreatic cancer","volume":"32","author":"Lu","year":"2015","journal-title":"Med. Oncol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/jgh.12668","article-title":"Chloride intracellular channel 1 participates in migration and invasion of hepatocellular carcinoma by targeting maspin","volume":"30","author":"Wei","year":"2015","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1007\/s13277-015-3052-8","article-title":"CLIC1 a novel biomarker of intraperitoneal metastasis in serous epithelial ovarian cancer","volume":"36","author":"Ye","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s11010-012-1271-5","article-title":"Regulation of colon cancer cell migration and invasion by CLIC1-mediated RVD","volume":"365","author":"Wang","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.canlet.2009.02.020","article-title":"Identification of metastasis-associated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1","volume":"281","author":"Wang","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"892","DOI":"10.4103\/0973-1482.154057","article-title":"CLIC1 overexpression is associated with poor prognosis in pancreatic ductal adenocarcinomas","volume":"12","author":"Jia","year":"2016","journal-title":"J. Cancer Res. Ther."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s13277-014-2606-5","article-title":"CLIC1 overexpression is associated with poor prognosis in gallbladder cancer","volume":"36","author":"Ding","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1756-9966-31-44","article-title":"Elevated expression of chloride intracellular channel 1 is correlated with poor prognosis in human gliomas","volume":"31","author":"Wang","year":"2012","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1111\/cas.13248","article-title":"Chloride intracellular channel 1 regulates the antineoplastic effects of metformin in gallbladder cancer cells","volume":"108","author":"Liu","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1158\/0008-5472.562.65.2","article-title":"Antisense suppression of the chloride intracellular channel family induces apoptosis, enhances tumor necrosis factor \u03b1-induced apoptosis, and inhibits tumor growth","volume":"65","author":"Suh","year":"2005","journal-title":"Cancer Res."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.3748\/wjg.v18.i24.3070","article-title":"Function of chloride intracellular channel 1 in gastric cancer cells","volume":"18","author":"Ma","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00232-006-0059-5","article-title":"The CLIC1 chloride channel is regulated by the cystic fibrosis transmembrane conductance regulator when expressed in Xenopus oocytes","volume":"213","author":"Edwards","year":"2006","journal-title":"J. Membr. Biol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"11252","DOI":"10.18632\/oncotarget.2617","article-title":"Metformin repositioning as antitumoral agent: Selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current","volume":"5","author":"Gritti","year":"2014","journal-title":"Oncotarget"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3892\/or.2014.3615","article-title":"CLC-3 channels in cancer (Review)","volume":"33","author":"Hong","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"100077","DOI":"10.1016\/j.waojou.2019.100077","article-title":"Calcium-activated chloride channel regulator 1 (CLCA1): More than a regulator of chloride transport and mucus production","volume":"12","author":"Liu","year":"2019","journal-title":"World Allergy Organ. J."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/4\/898\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:16:10Z","timestamp":1760174170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/4\/898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,7]]},"references-count":220,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["cancers12040898"],"URL":"https:\/\/doi.org\/10.3390\/cancers12040898","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,7]]}}}