{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:47:16Z","timestamp":1790214436295,"version":"4.1.0"},"reference-count":193,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"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>Calcium signaling is a fundamental regulator of cell physiology, controlling proliferation, differentiation, migration, metabolism, gene expression, and cell death. In cancer, these signaling pathways are extensively remodeled to generate spatially and temporally restricted Ca2+ signals that support malignant progression while avoiding calcium-induced cytotoxicity. PMCAs traditionally regarded as high-affinity calcium extrusion pumps, have recently emerged as multifunctional regulators of compartmentalized calcium signaling. In addition to maintaining low cytosolic Ca2+ concentrations, PMCA isoforms organize specialized signaling microdomains by interacting with receptors, ion channels, scaffold proteins, and downstream signaling molecules, thereby selectively modulating calcium-dependent pathways involved in tumor growth and metastasis. Accumulating evidence demonstrates that PMCA isoforms exert distinct, context-dependent functions in cancer. PMCA1 primarily contributes to basal calcium homeostasis but has also been implicated in tumor progression, angiogenesis, and regulation of the tumor immune microenvironment. PMCA2 promotes survival and oncogenic signaling in HER2-positive breast cancer through stabilization of receptor signaling complexes. PMCA3 has been linked mainly to endocrine tumors and selected malignancies, although mechanistic evidence remains limited. PMCA4 exhibits the greatest functional diversity, acting either as a tumor suppressor or a promoter depending on the cancer type by regulating localized calcium signaling, cell migration, invasion, differentiation, and interactions with oncogenic signaling networks. This review summarizes current advances in the structural biology, regulation, and signaling functions of PMCA isoforms, with particular emphasis on their emerging roles in cancer biology. We also discuss the potential of PMCAs as prognostic biomarkers and therapeutic targets, highlighting the importance of isoform-specific strategies for targeting calcium signaling in cancer.<\/jats:p>","DOI":"10.3390\/cancers18152450","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:09:42Z","timestamp":1785398982000},"page":"2450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Plasma Membrane Ca2+-ATPases in Cancer: Current Insights and Future Perspectives"],"prefix":"10.3390","volume":"18","author":[{"given":"Malwina","family":"Lisek","sequence":"first","affiliation":[{"name":"Department of Molecular Neurochemistry, Medical University of Lodz, 90-419 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Tomczak","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurochemistry, Medical University of Lodz, 90-419 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5887-1105","authenticated-orcid":false,"given":"Natalia","family":"Bochenska","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurochemistry, Medical University of Lodz, 90-419 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Duraj","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurochemistry, Medical University of Lodz, 90-419 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-9011","authenticated-orcid":false,"given":"Tomasz","family":"Boczek","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurochemistry, Medical University of Lodz, 90-419 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.tcb.2022.07.004","article-title":"Calcium homeostasis and cancer: Insights from endoplasmic reticulum-centered organelle communications","volume":"33","author":"Zheng","year":"2022","journal-title":"Trends Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10555-016-9634-0","article-title":"Calcium role in human carcinogenesis: A comprehensive analysis and critical review of literature","volume":"35","author":"Kadio","year":"2016","journal-title":"Cancer Metastasis Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100254","DOI":"10.1016\/j.mocell.2025.100254","article-title":"Crucial roles of calcium ATPases and phosphoinositides: Insights into pathophysiology and therapeutic strategies","volume":"48","author":"Gu","year":"2025","journal-title":"Mol. Cells"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1196\/annals.1387.023","article-title":"Plasma Membrane Ca2+ ATPases as Dynamic Regulators of Cellular Calcium Handling","volume":"1099","author":"Strehler","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_5","first-page":"a004168","article-title":"The Plasma Membrane Ca2+ ATPase and the Plasma Membrane Sodium Calcium Exchanger Cooperate in the Regulation of Cell Calcium","volume":"3","author":"Brini","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23380","DOI":"10.1074\/jbc.M113.470542","article-title":"Plasma Membrane Calcium ATPase Activity Is Regulated by Actin Oligomers through Direct Interaction","volume":"288","author":"Dalghi","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ceca.2017.06.001","article-title":"Metabolic regulation of the PMCA: Role in cell death and survival","volume":"69","author":"Bruce","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bbrc.2015.01.121","article-title":"Plasma membrane calcium ATPases: From generic Ca2+ sump pumps to versatile systems for fine-tuning cellular Ca2+","volume":"460","author":"Strehler","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"190","DOI":"10.18433\/J3Z011","article-title":"Plasma Membrane Calcium ATPases as Novel Candidates for Therapeutic Agent Development","volume":"16","author":"Strehler","year":"2013","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_10","unstructured":"Krebs, J. (2014, January 13\u201317). The plethora of PMCA isoforms: Alternative splicing and differential expression. Proceedings of the 13th International Meeting of the European Calcium Society, Centre de Congr\u00e8s, Aix-en-Provence, France."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.bbamcr.2015.12.011","article-title":"Multifaceted plasma membrane Ca2+ pumps: From structure to intracellular Ca2+ handling and cancer","volume":"1863","author":"Varga","year":"2016","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10863-024-10010-5","article-title":"Analysis of cholesterol-recognition motifs of the plasma membrane Ca2+-ATPase","volume":"56","year":"2024","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/nature11899","article-title":"Crystal structures of the calcium pump and sarcolipin in the Mg2+-bound E1 state","volume":"495","author":"Toyoshima","year":"2013","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1074\/jbc.M114.585828","article-title":"Modulation of plasma membrane Ca2+-ATPase by neutral phospholipids: Effect of the micelle-vesicle transition and the bilayer thickness","volume":"290","author":"Pignataro","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1016\/j.bbamem.2008.08.020","article-title":"High sensibility to reactivation by acidic lipids of the recombinant human plasma membrane Ca2+-ATPase isoform 4xb purified from Saccharomyces cerevisiae","volume":"1778","author":"Cura","year":"2008","journal-title":"Biochim. Biophys. Acta BBA\u2014Biomembr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1038\/nature06418","article-title":"The structural basis of calcium transport by the calcium pump","volume":"450","author":"Olesen","year":"2007","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39070","DOI":"10.1074\/jbc.M112.404434","article-title":"Nucleotide activation of the Ca-ATPase","volume":"287","author":"Autry","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41586-025-09402-3","article-title":"Molecular mechanism of ultrafast transport by plasma membrane Ca2+-ATPases","volume":"646","author":"Vinayagam","year":"2025","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fj.04-2549fje","article-title":"Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: A potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury","volume":"19","author":"Kurnellas","year":"2004","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1523\/JNEUROSCI.0069-07.2007","article-title":"Plasma Membrane Ca2+ ATPase 2 Contributes to Short-Term Synapse Plasticity at the Parallel Fiber to Purkinje Neuron Synapse","volume":"27","author":"Empson","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1152\/physrev.2001.81.1.21","article-title":"Role of Alternative Splicing in Generating Isoform Diversity Among Plasma Membrane Calcium Pumps","volume":"81","author":"Strehler","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1196\/annals.1387.029","article-title":"Distinct Phenotypes among Plasma Membrane Ca2+-ATPase Knockout Mice","volume":"1099","author":"Prasad","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0003-9861(81)90187-9","article-title":"Equimolar interaction between calmodulin and the Ca2+ ATPase from human erythrocyte membranes","volume":"210","author":"Graf","year":"1981","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1021\/bi602481u","article-title":"Mechanism of Calmodulin Recognition of the Binding Domain of Isoform 1b of the Plasma Membrane Ca2+-ATPase: Kinetic Pathway and Effects of Methionine Oxidation","volume":"46","author":"Slaughter","year":"2007","journal-title":"Biochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Fresneda, M., Lizano, E., Echeverr\u00eda-Garc\u00e9s, G., Herrera-Yela, A., Feij\u00f3o, D., Vivas-Colmenares, G.V., L\u00f3pez-Zaplana, A., Pedelini, L., Mendoza, M., and Navarro, J.C. (2025). Calmodulin Interaction Interface with Plasma Membrane Ca2+-ATPase Isoforms: An Integrative Bioinformatic Analysis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262311750"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s42003-018-0203-7","article-title":"Structural basis for activation of plasma-membrane Ca2+-ATPase by calmodulin","volume":"1","author":"Nitsche","year":"2018","journal-title":"Commun. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1016\/S0021-9258(18)45587-1","article-title":"The maximal velocity and the calcium affinity of the red cell calcium pump may be regulated independently","volume":"262","author":"Enyedi","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"39797","DOI":"10.1074\/jbc.M104380200","article-title":"The Plasma Membrane Calcium Pump Displays Memory of Past Calcium Spikes","volume":"276","author":"Caride","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29664","DOI":"10.1074\/jbc.M112.377556","article-title":"Alternative Pathways for Association and Dissociation of the Calmodulin-Binding Domain of Plasma Membrane Ca2+-ATPase Isoform 4b (PMCA4b)","volume":"287","author":"Penniston","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35227","DOI":"10.1074\/jbc.274.49.35227","article-title":"The Rate of Activation by Calmodulin of Isoform 4 of the Plasma Membrane Ca2+ Pump Is Slow and Is Changed by Alternative Splicing","volume":"274","author":"Caride","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1054\/ceca.2001.0212","article-title":"Delayed activation of the plasma membrane calcium pump by asudden increase in Ca2+: Fast pumps reside in fast cells","volume":"30","author":"Caride","year":"2001","journal-title":"Cell Calcium"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.1523\/JNEUROSCI.1962-06.2006","article-title":"Nonlinear [Ca2+] Signaling in Dendrites and Spines Caused by Activity-Dependent Depression of Ca2+ Extrusion","volume":"26","author":"Scheuss","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17981","DOI":"10.1074\/jbc.272.29.17981","article-title":"Plasma Membrane Ca2+ Pump Isoforms 2a and 2b Are Unusually Responsive to Calmodulin and Ca2+","volume":"272","author":"Elwess","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Krebs, J. (2022). Structure, Function and Regulation of the Plasma Membrane Calcium Pump in Health and Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031027"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0021-9258(17)42307-6","article-title":"The Ca2+ affinity of the plasma membrane Ca2+ pump is controlled by alternative splicing","volume":"269","author":"Enyedi","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1152\/physrev.00028.2016","article-title":"The Plasma Membrane Calcium ATPases and Their Role as Major New Players in Human Disease","volume":"97","author":"Stafford","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Marcos, D., Sepulveda, M.R., Berrocal, M., and Mata, A.M. (2009). Ontogeny of ATP hydrolysis and isoform expression of the Plasma Membrane Ca2+-ATPase in mouse brain. BMC Neurosci., 10.","DOI":"10.1186\/1471-2202-10-112"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1111\/j.1471-4159.1992.tb08476.x","article-title":"Expression of Plasma Membrane Calcium-Pumping ATPase mRNAs in Developing Rat Brain and Adult Brain Subregions: Evidence for Stage-Specific Expression","volume":"59","author":"Brandt","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0304-4165(99)00058-6","article-title":"Developmental expression of the four plasma membrane calcium ATPase (Pmca) genes in the mouse","volume":"1428","author":"Zacharias","year":"1999","journal-title":"Biochim. Biophys. Acta BBA\u2014Gen. Subj."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/dvdy.21131","article-title":"Developmental distribution of plasma membrane Ca2+-ATPase isoforms in chick cerebellum","volume":"236","author":"Marcos","year":"2007","journal-title":"Dev. Dyn."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/hipo.20129","article-title":"Changes in the expression of plasma membrane calcium extrusion systems during the maturation of hippocampal neurons","volume":"16","author":"Kip","year":"2005","journal-title":"Hippocampus"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/0006-2952(96)00046-9","article-title":"Tissue-specific developmental regulation of protein kinase C isoforms","volume":"51","author":"Goldberg","year":"1996","journal-title":"Biochem. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1007\/BF02430603","article-title":"Proteolipids in developing rat brain","volume":"10","author":"Manukian","year":"1985","journal-title":"Neurochem. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1091\/mbc.2.10.819","article-title":"Developmental regulation of calmodulin gene expression in rat brain and skeletal muscle","volume":"2","author":"Weinman","year":"1991","journal-title":"Cell Regul."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ceca.2012.08.002","article-title":"Downregulation of PMCA2 or PMCA3 reorganizes Ca2+ handling systems in differentiating PC12 cells","volume":"52","author":"Boczek","year":"2012","journal-title":"Cell Calcium"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1196\/annals.1387.008","article-title":"Functional Importance of PMCA Isoforms in Growth and Development of PC12 Cells","volume":"1099","author":"Zylinska","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1080\/14734220310022289","article-title":"Distribution of calcium-binding proteins in the cerebellum","volume":"2","author":"Bastianelli","year":"2003","journal-title":"Cerebellum"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/j.0953-816X.2003.03156.x","article-title":"Localization of endoplasmic reticulum and plasma membrane Ca2+-ATPases in subcellular fractions and sections of pig cerebellum","volume":"19","author":"Mata","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1111\/j.1471-4159.2007.04794.x","article-title":"Functional and immunocytochemical evidence for the expression and localization of the secretory pathway Ca2+-ATPase isoform 1 (SPCA1) in cerebellum relative to other Ca2+ pumps","volume":"103","author":"Berrocal","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.neuroscience.2010.05.062","article-title":"A plasma membrane Ca2+ ATPase isoform at the postsynaptic density","volume":"169","author":"Burette","year":"2010","journal-title":"Neuroscience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1002\/cne.22409","article-title":"Cellular and subcellular localization of the neuron-specific plasma membrane calcium ATPase PMCA1a in the rat brain","volume":"518","author":"Kenyon","year":"2010","journal-title":"J. Comp. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ceca.2006.06.004","article-title":"Cellular and subcellular localization of Na+\u2013Ca2+ exchanger protein isoforms, NCX1, NCX2, and NCX3 in cerebral cortex and hippocampus of adult rat","volume":"41","author":"Minelli","year":"2007","journal-title":"Cell Calcium"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1529\/biophysj.105.072470","article-title":"A Model of the Roles of Essential Kinases in the Induction and Expression of Late Long-Term Potentiation","volume":"90","author":"Smolen","year":"2006","journal-title":"Biophys. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0197-4580(98)00078-5","article-title":"Age-related decrease in brain synaptic membrane Ca2+-ATPase in F344\/BNF1 rats","volume":"19","author":"Zaidi","year":"1998","journal-title":"Neurobiol. Aging"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0047-6374(84)90142-8","article-title":"Age-dependent alterations in synaptic membrane systems for Ca2+ regulation","volume":"25","author":"Michaelis","year":"1984","journal-title":"Mech. Ageing Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0197-0186(99)00062-5","article-title":"Distribution of plasma membrane Ca2+ pump (PMCA) isoforms in the gerbil brain: Effect of ischemia-reperfusion injury","volume":"35","author":"Raeymaekers","year":"1999","journal-title":"Neurochem. Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1096\/fj.08-121459","article-title":"Altered Ca2+ dependence of synaptosomal plasma membrane Ca2+-ATPase in human brain affected by Alzheimer\u2019s disease","volume":"23","author":"Berrocal","year":"2009","journal-title":"FASEB J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.bbadis.2015.04.007","article-title":"Inhibition of PMCA activity by tau as a function of aging and Alzheimer\u2019s neuropathology","volume":"1852","author":"Berrocal","year":"2015","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Basis Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1093\/hmg\/ddm133","article-title":"Mutant huntingtin\u2019s effects on striatal gene expression in mice recapitulate changes observed in human Huntington\u2019s disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage","volume":"16","author":"Kuhn","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1469-7793.1998.159bx.x","article-title":"Calcium permeation of the turtle hair cell mechanotransducer channel and its relation to the composition of endolymph","volume":"506","author":"Ricci","year":"1998","journal-title":"J. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8261","DOI":"10.1523\/JNEUROSCI.18-20-08261.1998","article-title":"The Endogenous Calcium Buffer and the Time Course of Transducer Adaptation in Auditory Hair Cells","volume":"18","author":"Ricci","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6300","DOI":"10.1523\/JNEUROSCI.18-16-06300.1998","article-title":"Regulation of Free Ca2+Concentration in Hair-Cell Stereocilia","volume":"18","author":"Lumpkin","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0378-5955(96)00132-3","article-title":"Identification and cloning of site C splice variants of plasma membrane Ca-ATPase in the gerbil cochlea","volume":"101","author":"Crouch","year":"1996","journal-title":"Hear. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0378-5955(98)00091-4","article-title":"Evidence for differential regulation of calcium by outer versus inner hair cells: Plasma membrane Ca-ATPase gene expression","volume":"123","author":"Furuta","year":"1998","journal-title":"Hear. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1523\/JNEUROSCI.18-02-00610.1998","article-title":"Plasma Membrane Ca2+-ATPase Extrudes Ca2+ from Hair Cell Stereocilia","volume":"18","author":"Yamoah","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7131","DOI":"10.1523\/JNEUROSCI.20-19-07131.2000","article-title":"Active Hair Bundle Motion Linked to Fast Transducer Adaptation in Auditory Hair Cells","volume":"20","author":"Ricci","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1523\/JNEUROSCI.22-01-00044.2002","article-title":"Mechanisms of Active Hair Bundle Motion in Auditory Hair Cells","volume":"22","author":"Ricci","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neulet.2017.09.059","article-title":"PMCA2 pump mutations and hereditary deafness","volume":"663","author":"Bortolozzi","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1007\/s11427-011-4200-z","article-title":"The plasma membrane calcium pump in the hearing process: Physiology and pathology","volume":"54","author":"Carafoli","year":"2011","journal-title":"Sci. China Life Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"18693","DOI":"10.1074\/jbc.273.30.18693","article-title":"Balance and Hearing Deficits in Mice with a Null Mutation in the Gene Encoding Plasma Membrane Ca2+-ATPase Isoform 2","volume":"273","author":"Kozel","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"37693","DOI":"10.1074\/jbc.M110.170092","article-title":"The Novel PMCA2 Pump Mutation Tommy Impairs Cytosolic Calcium Clearance in Hair Cells and Links to Deafness in Mice","volume":"285","author":"Bortolozzi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1073\/pnas.0609775104","article-title":"A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness","volume":"104","author":"Ficarella","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Spiden, S.L., Bortolozzi, M., Di Leva, F., De Angelis, M.H., Fuchs, H., Lim, D., Ortolano, S., Ingham, N.J., Brini, M., and Carafoli, E. (2008). The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000238"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"C1595","DOI":"10.1152\/ajpcell.2000.279.5.C1595","article-title":"Ca2+-ATPase protein expression in mammary tissue","volume":"279","author":"Reinhardt","year":"2000","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"42369","DOI":"10.1074\/jbc.M407788200","article-title":"Null Mutation in the Gene Encoding Plasma Membrane Ca2+-ATPase Isoform 2 Impairs Calcium Transport into Milk","volume":"279","author":"Reinhardt","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.bbrc.2008.03.003","article-title":"Localization of plasma membrane and secretory calcium pumps in the mammary gland","volume":"369","author":"Faddy","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.bbrc.2008.11.004","article-title":"Mammary gland involution is associated with rapid down regulation of major mammary Ca2+-ATPases","volume":"378","author":"Reinhardt","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"11405","DOI":"10.1073\/pnas.0911186107","article-title":"PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer","volume":"107","author":"VanHouten","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"18464","DOI":"10.1074\/jbc.M301482200","article-title":"Alternative Splicing of the First Intracellular Loop of Plasma Membrane Ca2+-ATPase Isoform 2 Alters Its Membrane Targeting","volume":"278","author":"Chicka","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bbrc.2011.05.147","article-title":"Apical localization of PMCA2w\/b is enhanced in terminally polarized MDCK cells","volume":"410","author":"Antalffy","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ceca.2011.12.010","article-title":"Plasma membrane calcium pump (PMCA) isoform 4 is targeted to the apical membrane by the w-splice insert from PMCA2","volume":"51","author":"Antalffy","year":"2012","journal-title":"Cell Calcium"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"F363","DOI":"10.1152\/ajprenal.00076.2003","article-title":"Vitamin D3upregulates plasma membrane Ca2+-ATPase expression and potentiates apico-basal Ca2+flux in MDCK cells","volume":"286","author":"Kip","year":"2004","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"15771","DOI":"10.1074\/jbc.272.25.15771","article-title":"Polarized expression of Ca2+ pumps in pancreatic and salivary gland cells. Role in initiation and propagation of [Ca2+]i waves","volume":"272","author":"Lee","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s42003-025-07814-5","article-title":"The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation","volume":"8","author":"Papp","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1161\/HYPERTENSIONAHA.110.165068","article-title":"Mice Lacking Hypertension Candidate Gene ATP2B1 in Vascular Smooth Muscle Cells Show Significant Blood Pressure Elevation","volume":"59","author":"Kobayashi","year":"2012","journal-title":"Hypertension"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"C1239","DOI":"10.1152\/ajpcell.00440.2005","article-title":"Role of plasma membrane Ca2+-ATPase in contraction-relaxation processes of the bladder: Evidence from PMCA gene-ablated mice","volume":"290","author":"Liu","year":"2006","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1161\/HYPERTENSIONAHA.110.153429","article-title":"Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: The Japanese Millennium Genome Project","volume":"56","author":"Tabara","year":"2010","journal-title":"Hypertension"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/ng.384","article-title":"Genome-wide association study of blood pressure and hypertension","volume":"41","author":"Levy","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/MNH.0b013e32835da4ca","article-title":"ATP2B1 and blood pressure: From associations to pathophysiology","volume":"22","author":"Hirawa","year":"2013","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.yjmcc.2022.07.011","article-title":"Cardiomyocyte-specific loss of plasma membrane calcium ATPase 1 impacts cardiac rhythm and is associated with ventricular repolarisation dysfunction","volume":"172","author":"Wilson","year":"2022","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"33742","DOI":"10.1074\/jbc.M404628200","article-title":"Targeted Ablation of Plasma Membrane Ca2+-ATPase (PMCA) 1 and 4 Indicates a Major Housekeeping Function for PMCA1 and a Critical Role in Hyperactivated Sperm Motility and Male Fertility for PMCA4","volume":"279","author":"Okunade","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"28220","DOI":"10.1074\/jbc.M312599200","article-title":"Plasma Membrane Ca2+ ATPase 4 Is Required for Sperm Motility and Male Fertility","volume":"279","author":"Schuh","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1095\/biolreprod.113.108712","article-title":"Plasma Membrane Ca2+-ATPase 4 in Murine Epididymis: Secretion of Splice Variants in the Luminal Fluid and a Role in Sperm Maturation1","volume":"89","author":"Patel","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4331\/wjbc.v1.i6.201","article-title":"Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways","volume":"1","author":"Holton","year":"2010","journal-title":"World J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0143-4160(03)00047-2","article-title":"Localization and regulation of Ca2+ entry and exit pathways in exocrine gland cells","volume":"33","author":"Petersen","year":"2003","journal-title":"Cell Calcium"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1016\/S0021-9258(19)50560-9","article-title":"Acetylcholine-evoked increase in the cytoplasmic Ca2+ concentration and Ca2+ extrusion measured simultaneously in single mouse pancreatic acinar cells","volume":"267","author":"Tepikin","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"14073","DOI":"10.1016\/S0021-9258(19)49680-4","article-title":"Pulsatile Ca2+ extrusion from single pancreatic acinar cells during receptor-activated cytosolic Ca2+ spiking","volume":"267","author":"Tepikin","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7615","DOI":"10.1074\/jbc.271.13.7615","article-title":"Localization of Ca2+ Extrusion Sites in Pancreatic Acinar Cells","volume":"271","author":"Belan","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/0092-8674(93)90513-P","article-title":"Local and global cytosolic Ca2+ oscillations in exocrine cells evoked by agonists and inositol trisphosphate","volume":"74","author":"Thorn","year":"1993","journal-title":"Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1083\/jcb.120.5.1147","article-title":"Calcium pump of the plasma membrane is localized in caveolae","volume":"120","author":"Fujimoto","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1073\/pnas.92.5.1759","article-title":"Caveolae from luminal plasmalemma of rat lung endothelium: Microdomains enriched in caveolin, Ca2+-ATPase, and inositol trisphosphate receptor","volume":"92","author":"Schnitzer","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4161\/cib.4.3.15040","article-title":"Regulation of apical membrane enrichment and retention of plasma membrane Ca2+ATPase splice variants by the PDZ-domain protein NHERF2","volume":"4","author":"Enyedi","year":"2011","journal-title":"Commun. Integr. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4426","DOI":"10.1073\/pnas.96.8.4426","article-title":"Hormone-induced secretory and nuclear translocation of calmodulin: Oscillations of calmodulin concentration with the nucleus as an integrator","volume":"96","author":"Craske","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.semcdb.2011.09.006","article-title":"Spatial organization of intracellular Ca2+ signals","volume":"23","author":"Konieczny","year":"2012","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Lisek, M., Ferenc, B., Studzian, M., Pulaski, L., Guo, F., Zylinska, L., and Boczek, T. (2017). Glutamate Deregulation in Ketamine-Induced Psychosis\u2014A Potential Role of PSD95, NMDA Receptor and PMCA Interaction. Front. Cell. Neurosci., 11.","DOI":"10.3389\/fncel.2017.00181"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Boczek, T., Sobolczyk, M., Mackiewicz, J., Lisek, M., Ferenc, B., Guo, F., and Zylinska, L. (2021). Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062785"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.bbamcr.2010.12.007","article-title":"Local signals with global impacts and clinical implications: Lessons from the plasma membrane calcium pump (PMCA4)","volume":"1813","author":"Oceandy","year":"2011","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Cell Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1083\/jcb.200104131","article-title":"The plasmamembrane calmodulin-dependent calcium pump: A major regulator of nitric oxide synthase I","volume":"155","author":"Schuh","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1016\/j.febslet.2007.07.054","article-title":"The interaction between endogenous calcineurin and the plasma membrane calcium-dependent ATPase is isoform specific in breast cancer cells","volume":"581","author":"Holton","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.bbagrm.2017.01.012","article-title":"Cross talk among PMCA, calcineurin and NFAT transcription factors in control of calmodulin gene expression in differentiating PC12 cells","volume":"1860","author":"Boczek","year":"2017","journal-title":"Biochim. Biophys. Acta BBA\u2014Gene Regul. Mech."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Boczek, T., Radzik, T., Ferenc, B., and Zylinska, L. (2019). The Puzzling Role of Neuron-Specific PMCA Isoforms in the Aging Process. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246338"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5081021","DOI":"10.1155\/2016\/5081021","article-title":"The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases","volume":"2016","author":"Kipanyula","year":"2016","journal-title":"J. Aging Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1161\/ATVBAHA.114.304363","article-title":"Plasma Membrane Calcium ATPase Isoform 4 Inhibits Vascular Endothelial Growth Factor\u2013Mediated Angiogenesis Through Interaction with Calcineurin","volume":"34","author":"Baggott","year":"2014","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Park, Y.-J., Yoo, S.-A., Kim, M., and Kim, W.-U. (2020). The Role of Calcium\u2013Calcineurin\u2013NFAT Signaling Pathway in Health and Autoimmune Diseases. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00195"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cne.10281","article-title":"Cell-specific expression of plasma membrane calcium ATPase isoforms in retinal neurons","volume":"451","author":"Krizaj","year":"2002","journal-title":"J. Comp. Neurol."},{"key":"ref_116","first-page":"2828","article-title":"Calcineurin activation causes retinal ganglion cell degeneration","volume":"18","author":"Qu","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"9383","DOI":"10.1007\/s12035-024-04129-0","article-title":"NFATc4 Knockout Promotes Neuroprotection and Retinal Ganglion Cell Regeneration After Optic Nerve Injury","volume":"61","author":"Mackiewicz","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Sritangos, P., Alarcon, E.P., James, A.D., Sultan, A., Richardson, D.A., and Bruce, J.I.E. (2020). Plasma Membrane Ca. Cancers, 12.","DOI":"10.3390\/cancers12010218"},{"key":"ref_119","first-page":"ra19","article-title":"Plasma membrane Ca2+-ATPases can shape the pattern of Ca2+ transients induced by store-operated Ca2+ entry","volume":"8","author":"Caride","year":"2015","journal-title":"Sci. Signal."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Merino-Wong, M., Niemeyer, B.A., and Alansary, D. (2021). Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4+ T-Cell Compartments. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.687242"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"11074","DOI":"10.1038\/ncomms11074","article-title":"The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy","volume":"7","author":"Mohamed","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/nature19356","article-title":"High-throughput discovery of novel developmental phenotypes","volume":"537","author":"Dickinson","year":"2016","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41431-023-01484-9","article-title":"Biallelic ATP2B1 variants as a likely cause of a novel neurodevelopmental malformation syndrome with primary hypoparathyroidism","volume":"32","author":"Yap","year":"2023","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_124","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_125","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1038\/sj.onc.1205460","article-title":"Identification of a novel gene NCRMS on chromosome 12q21 with differential expression between Rhabdomyosarcoma subtypes","volume":"21","author":"Chan","year":"2002","journal-title":"Oncogene"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/S0898-6568(02)00049-9","article-title":"Expression of plasma membrane calcium pump isoform mRNAs in breast cancer cell lines","volume":"14","author":"Lee","year":"2002","journal-title":"Cell. Signal."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.yjmcc.2021.03.011","article-title":"Plasma membrane calcium ATPase 1 regulates human umbilical vein endothelial cell angiogenesis and viability","volume":"156","author":"Njegic","year":"2021","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Zhang, X., He, Y., Ren, P., Chen, L., Han, Z., Qi, L., Chen, L., Luo, Y., Zhang, N., and Lu, W. (2022). Low expression and Hypermethylation of ATP2B1 in Intrahepatic Cholangiocarcinoma Correlated with Cold Tumor Microenvironment. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.927298"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Chen, L., and Tian, X. (2026). Abstract 7906: Integrated multi-omics profiling identifies an immunotherapy vulnerable and prognostic associated subtype in cholangiocarcinoma. Cancer Res., 86.","DOI":"10.1158\/1538-7445.AM2026-7906"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Khoshbakht, S., Mokhtari, M., Moravveji, S.S., Jamalkandi, S.A., and Masoudi-Nejad, A. (2022). Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression. BMC Genet., 23.","DOI":"10.1186\/s12863-021-01015-9"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Hu, J., Song, Y., Cai, X., Halina, H., Qiao, K., Lu, J., Yin, C., and Gao, F. (2023). A novel pyroptosis gene expression-based risk score for survival in gastric cancer. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1120216"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Zhao, X., Tian, Z., and Liu, L. (2021). circATP2B1 Promotes Aerobic Glycolysis in Gastric Cancer Cells Through Regulation of the miR-326 Gene Cluster. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.628624"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13019-024-02507-2","article-title":"Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression","volume":"19","author":"Chen","year":"2024","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"14499","DOI":"10.1038\/s41598-023-41495-6","article-title":"Identification of m5C-related lncRNAs signature to predict prognosis and therapeutic responses in esophageal squamous cell carcinoma patients","volume":"13","author":"Ma","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Dong, X., Liao, P., Liu, X., Yang, Z., Wang, Y., Zhong, W., and Wang, B. (2023). Construction and Validation of a Reliable Disulfidptosis-Related LncRNAs Signature of the Subtype, Prognostic, and Immune Landscape in Colon Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612915"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1038\/s41598-022-06934-w","article-title":"Weighted correlation network analysis revealed novel long non-coding RNAs for colorectal cancer","volume":"12","author":"Khameneh","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e2604380123","DOI":"10.1073\/pnas.2604380123","article-title":"ATP2B1 expression identifies human hematopoietic stem cells with superior repopulation and self-renewal","volume":"123","author":"Varesi","year":"2026","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/978-1-4020-6191-2_13","article-title":"The plasma membrane calcium ATPase and disease","volume":"45","author":"Tempel","year":"2007","journal-title":"Subcell. Biochem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.bbrc.2005.09.119","article-title":"Plasma membrane calcium-ATPase 2 and 4 in human breast cancer cell lines","volume":"337","author":"Lee","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"25505","DOI":"10.1038\/srep25505","article-title":"The calcium pump plasma membrane Ca2+-ATPase 2 (PMCA2) regulates breast cancer cell proliferation and sensitivity to doxorubicin","volume":"6","author":"Peters","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1016\/j.bbrc.2016.09.030","article-title":"PMCA2 silencing potentiates MDA-MB-231 breast cancer cell death initiated with the Bcl-2 inhibitor ABT-263","volume":"478","author":"Curry","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.beem.2013.02.011","article-title":"The calcium-sensing receptor in the breast","volume":"27","author":"Vanhouten","year":"2013","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.tem.2013.08.004","article-title":"New concepts of breast cell communication to bone","volume":"25","author":"Horseman","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"E282","DOI":"10.1073\/pnas.1516138113","article-title":"PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer","volume":"113","author":"Jeong","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12041-024-01487-5","article-title":"YY1 as a mediator to enhance the resistance of KRAS mutant colorectal cancer cells to cetuximab","volume":"104","author":"Ma","year":"2024","journal-title":"J. Genet."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Jeong, J., Kim, W., Kim, L.K., VanHouten, J., and Wysolmerski, J.J. (2017). HER2 signaling regulates HER2 localization and membrane retention. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0174849"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"6555","DOI":"10.1074\/jbc.M116.770883","article-title":"The scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2","volume":"292","author":"Jeong","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1074\/jbc.RA118.004143","article-title":"Inhibition of ezrin causes PKC\u03b1-mediated internalization of erbb2\/HER2 tyrosine kinase in breast cancer cells","volume":"294","author":"Jeong","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13058-025-02025-6","article-title":"Erbin interacts with NHERF1 and Ezrin to stabilize a membrane ErbB2 signaling complex in HER2-positive breast cancer","volume":"27","author":"Jeong","year":"2025","journal-title":"Breast Cancer Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1007\/s12015-026-11124-6","article-title":"A Stem Cell\u2013Osteogenesis Axis in Malignant Breast Calcification: SQLE-Driven Reprogramming of Adipose-Derived Mesenchymal Stem Cells","volume":"22","author":"Wu","year":"2026","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_151","first-page":"6950","article-title":"Differential expression of PMCA2 mRNA isoforms in a cohort of Spanish patients with breast tumor types","volume":"16","author":"Gaibar","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Kosiorek, M., Zylinska, L., Zablocki, K., and Pikula, S. (2014). Calcineurin\/NFAT Signaling Represses Genes Vamp1 and Vamp2 via PMCA-Dependent Mechanism during Dopamine Secretion by Pheochromocytoma Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092176"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11010-011-1047-3","article-title":"Gene expression pattern in PC12 cells with reduced PMCA2 or PMCA3 isoform: Selective up-regulation of calmodulin and neuromodulin","volume":"360","author":"Boczek","year":"2011","journal-title":"Mol. Cell. Biochem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1093\/carcin\/bgs282","article-title":"Disruption of the interaction between PMCA2 and calcineurin triggers apoptosis and enhances paclitaxel-induced cytotoxicity in breast cancer cells","volume":"33","author":"Baggott","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e2317141121","DOI":"10.1073\/pnas.2317141121","article-title":"Malignant tumor cells engender second membrane-lined organelles for self-protection and tumor progression","volume":"121","author":"Yi","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13062-025-00702-2","article-title":"Plasma membrane calcium ATPases and cerebellar pathology: What\u2019s the role in the ataxia?","volume":"20","author":"Peggion","year":"2025","journal-title":"Biol. Direct"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neuron.2016.02.032","article-title":"Involvement of Ca2+-Dependent Hyperpolarization in Sleep Duration in Mammals","volume":"90","author":"Tatsuki","year":"2016","journal-title":"Neuron"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.1210\/jc.2018-01004","article-title":"Targeted Molecular Characterization of Aldosterone-Producing Adenomas in White Americans","volume":"103","author":"Nanba","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1161\/HYPERTENSIONAHA.118.12070","article-title":"Genetic Characteristics of Aldosterone-Producing Adenomas in Blacks","volume":"73","author":"Nanba","year":"2019","journal-title":"Hypertension"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e151","DOI":"10.1016\/j.lpm.2018.07.006","article-title":"Molecular genetics of Conn adenomas in the era of exome analysis","volume":"47","author":"Boulkroun","year":"2018","journal-title":"Presse M\u00e9d."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Liao, H.-W., Peng, K.-Y., Wu, V.-C., Lin, Y.-H., Lin, S.-L., Lin, W.-C., Chueh, J.S., and on behalf of (TAIPAI) Study Group (2021). Characteristics of a Novel ATP2B3 K416_F418delinsN Mutation in a Classical Aldosterone-Producing Adenoma. Cancers, 13.","DOI":"10.3390\/cancers13184729"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e250228","DOI":"10.20945\/2359-4292-2025-0228","article-title":"Molecular investigation of primary aldosteronism: Exploring genetic heterogeneity in understudied populations","volume":"69","author":"Maeda","year":"2025","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1210\/clinem\/dgag002","article-title":"Somatic Drivers in Aldosterone-Producing Adenomas and Nodules: Insights from a Brazilian Cohort of Primary Aldosteronism","volume":"111","author":"Guimaraes","year":"2026","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1161\/HYPERTENSIONAHA.117.09057","article-title":"Aldosterone-Producing Adenomas: Histopathology-Genotype Correlation and Identification of a Novel","volume":"70","author":"Tan","year":"2017","journal-title":"Hypertension"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"6269","DOI":"10.1038\/s41598-019-41525-2","article-title":"RNA Sequencing Provides Novel Insights into the Transcriptome of Aldosterone Producing Adenomas","volume":"9","author":"Backman","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e3224","DOI":"10.1210\/clinem\/dgaa367","article-title":"Biochemical, Histopathological, and Genetic Characterization of Posture-Responsive and Unresponsive APAs","volume":"105","author":"Guo","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e4066","DOI":"10.1210\/clinem\/dgaa595","article-title":"Prevalence of Somatic Mutations in Aldosterone-Producing Adenomas in Japanese Patients","volume":"105","author":"Nanba","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"105414","DOI":"10.1016\/j.jsbmb.2019.105414","article-title":"Genomics of benign adrenocortical tumors","volume":"193","author":"Jouinot","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1055\/s-0043-120066","article-title":"Unanswered Questions in the Genetic Basis of Primary Aldosteronism","volume":"49","author":"Scholl","year":"2017","journal-title":"Horm. Metab. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"106116","DOI":"10.1016\/j.jsbmb.2022.106116","article-title":"Phenotype-genotype correlation in aldosterone-producing adenomas characterized by intracellular cholesterol metabolism","volume":"221","author":"Harashima","year":"2022","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Lim, J.S., Plaska, S.W., Rege, J., Rainey, W.E., and Turcu, A.F. (2021). Aldosterone-Regulating Receptors and Aldosterone-Driver Somatic Mutations. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.644382"},{"key":"ref_172","first-page":"52","article-title":"Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism","volume":"11","author":"Hattangady","year":"2020","journal-title":"Discov. Oncol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s12672-024-01653-2","article-title":"Identification of critical biomarkers and immune landscape patterns in glioma based on multi-database","volume":"16","author":"Yuan","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1080\/19768354.2020.1760932","article-title":"Construction and validation of a seven-gene signature for predicting overall survival in patients with kidney renal clear cell carcinoma via an integrated bioinformatics analysis","volume":"24","author":"Jiang","year":"2020","journal-title":"Anim. Cells Syst."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.mce.2005.12.028","article-title":"Sperm phenotype of mice carrying a gene deletion for the plasma membrane calcium\/calmodulin dependent ATPase 4","volume":"250","author":"Withers","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/ni1072","article-title":"CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity","volume":"5","author":"Chen","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"C423","DOI":"10.1152\/ajpcell.00313.2006","article-title":"Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle: Evidence from PMCA gene-ablated mice","volume":"292","author":"Liu","year":"2007","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ceca.2013.12.003","article-title":"Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells","volume":"55","author":"Varga","year":"2014","journal-title":"Cell Calcium"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.bbrc.2015.06.113","article-title":"Selective upregulation of the expression of plasma membrane calcium ATPase isoforms upon differentiation and 1,25(OH)2D3-vitamin treatment of colon cancer cells","volume":"464","author":"Ribiczey","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1093\/carcin\/bgp223","article-title":"Plasma membrane calcium ATPase 4 and the remodeling of calcium homeostasis in human colon cancer cells","volume":"30","author":"Aung","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.gene.2014.02.050","article-title":"Investigation of the association between ATP2B4 and ATP5B genes with colorectal cancer","volume":"540","author":"Geyik","year":"2014","journal-title":"Gene"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1002\/ijc.30503","article-title":"The plasma membrane Ca2+ pump PMCA4b inhibits the migratory and metastatic activity of BRAF mutant melanoma cells","volume":"140","author":"Garay","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Heged\u00fcs, L., Pad\u00e1nyi, R., Moln\u00e1r, J., P\u00e1szty, K., Varga, K., Kenessey, I., S\u00e1rk\u00f6zy, E., Wolf, M., Grusch, M., and Hegyi, Z. (2017). Histone Deacetylase Inhibitor Treatment Increases the Expression of the Plasma Membrane Ca2+ Pump PMCA4b and Inhibits the Migration of Melanoma Cells Independent of ERK. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00095"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Heged\u00fcs, L., Livingstone, E., B\u00e1nkfalvi, \u00c1., Viehof, J., Enyedi, \u00c1., Bilecz, \u00c1., Gy\u0151rffy, B., Baranyi, M., T\u0151k\u00e9s, A.-M., and Gil, J. (2022). The Prognostic Relevance of PMCA4 Expression in Melanoma: Gender Specificity and Implications for Immune Checkpoint Inhibition. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063324"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1001\/jamadermatol.2015.2524","article-title":"Pigment-Synthesizing Melanocytic Neoplasm with Protein Kinase C Alpha (PRKCA) Fusion","volume":"152","author":"Bahrami","year":"2016","journal-title":"JAMA Dermatol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"zqad035","DOI":"10.1093\/function\/zqad035","article-title":"Driver Mutations of Pancreatic Cancer Affect Ca2+ Signaling and ATP Production","volume":"4","author":"Stopa","year":"2023","journal-title":"Function"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"353","DOI":"10.4149\/gpb_2019013","article-title":"Calcium homeostasis in cisplatin resistant epithelial ovarian cancer","volume":"38","author":"Kucukkaya","year":"2019","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1111\/1440-1681.13295","article-title":"Iron alters Ca2+ homeostasis in doxorubicin-resistant K562 cells","volume":"47","author":"Yalcintepe","year":"2020","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"118833","DOI":"10.1016\/j.bbamcr.2020.118833","article-title":"The calcium pump PMCA4 prevents epithelial-mesenchymal transition by inhibiting NFATc1-ZEB1 pathway in gastric cancer","volume":"1867","author":"Wang","year":"2020","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Cell Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"103050","DOI":"10.1016\/j.ceca.2025.103050","article-title":"GAT3-dependent regulation of glioma invasiveness via a lipid raft-associated PMCA4 Ca2+ transporter and a downstream CaMKII\/CREB signaling\u2014Implications for compartmentalized signaling in glioma tumors","volume":"130","author":"Kapsa","year":"2025","journal-title":"Cell Calcium"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s13046-020-01607-w","article-title":"ACYP2 contributes to malignant progression of glioma through promoting Ca2+ efflux and subsequently activating c-Myc and STAT3 signals","volume":"39","author":"Li","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.4049\/jimmunol.1501889","article-title":"Association of CD147 and Calcium Exporter PMCA4 Uncouples IL-2 Expression from Early TCR Signaling","volume":"196","author":"Supper","year":"2016","journal-title":"J. Immunol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"C1027","DOI":"10.1152\/ajpcell.2001.280.4.C1027","article-title":"Caloxin: A novel plasma membrane Ca2+pump inhibitor","volume":"280","author":"Chaudhary","year":"2001","journal-title":"Am. J. Physiol. Physiol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:23:47Z","timestamp":1785399827000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":193,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18152450"],"URL":"https:\/\/doi.org\/10.3390\/cancers18152450","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}