{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:48:51Z","timestamp":1769093331786,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian University and Research Ministry","award":["2017R5ZE2C"],"award-info":[{"award-number":["2017R5ZE2C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyponatremia is the prevalent electrolyte imbalance in cancer patients, and it is associated with a worse outcome. Notably, emerging clinical evidence suggests that hyponatremia adversely influences the response to anticancer treatments. Therefore, this study aims to investigate how reduced extracellular [Na+] affects the responsiveness of different cancer cell lines (from human colon adenocarcinoma, neuroblastoma, and small cell lung cancer) to cisplatin and the underlying potential mechanisms. Cisplatin dose\u2013response curves revealed higher IC50 in low [Na+] than normal [Na+]. Accordingly, cisplatin treatment was less effective in counteracting the proliferation and migration of tumor cells when cultured in low [Na+], as demonstrated by colony formation and invasion assays. In addition, the expression analysis of proteins involved in autophagosome\u2013lysosome formation and the visualization of lysosomal areas by electron microscopy revealed that one of the main mechanisms involved in chemoresistance to cisplatin is the promotion of autophagy. In conclusion, our data first demonstrate that the antitumoral effect of cisplatin is markedly reduced in low [Na+] and that autophagy is an important mechanism of drug escape. This study indicates the role of hyponatremia in cisplatin chemoresistance and reinforces the recommendation to correct this electrolyte alteration in cancer patients.<\/jats:p>","DOI":"10.3390\/ijms25084377","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T08:41:06Z","timestamp":1713256866000},"page":"4377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Reduced Extracellular Sodium Concentrations on Cisplatin Treatment in Human Tumor Cells: The Role of Autophagy"],"prefix":"10.3390","volume":"25","author":[{"given":"Laura","family":"Naldi","sequence":"first","affiliation":[{"name":"Endocrinology, Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, Careggi University Hospital, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Fibbi","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, Careggi University Hospital, University of Florence, 50139 Florence, Italy"},{"name":"Pituitary Diseases and Sodium Alterations Unit, Careggi University Hospital, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Anceschi","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, Careggi University Hospital, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2374-5147","authenticated-orcid":false,"given":"Patrizia","family":"Nardini","sequence":"additional","affiliation":[{"name":"Research Unit of Histology & Embryology, Department of Experimental & Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Guasti","sequence":"additional","affiliation":[{"name":"Research Unit of Histology & Embryology, Department of Experimental & Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-434X","authenticated-orcid":false,"given":"Alessandro","family":"Peri","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, Careggi University Hospital, University of Florence, 50139 Florence, Italy"},{"name":"Pituitary Diseases and Sodium Alterations Unit, Careggi University Hospital, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6611-8103","authenticated-orcid":false,"given":"Giada","family":"Marroncini","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, Careggi University Hospital, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1056\/NEJM200005253422107","article-title":"Hyponatremia","volume":"342","author":"Madias","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1056\/NEJM200005183422006","article-title":"Hypernatremia","volume":"342","author":"Madias","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1053\/j.ajkd.2011.08.029","article-title":"Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes","volume":"59","author":"Doshi","year":"2012","journal-title":"Am. J. Kidney Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fibbi, B., Marroncini, G., Naldi, L., Anceschi, C., Errico, A., Norello, D., and Peri, A. (2023). Hyponatremia and Cancer: From Bedside to Benchside. Cancers, 15.","DOI":"10.3390\/cancers15041197"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1365-2796.1995.tb00907.x","article-title":"Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease","volume":"238","author":"Andersen","year":"1995","journal-title":"J. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1007\/s00280-017-3392-8","article-title":"Electrolyte disorders with platinum-based chemotherapy: Mechanisms, manifestations and management","volume":"80","author":"Oronsky","year":"2017","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Berardi, R., Santoni, M., Rinaldi, S., Nunzi, E., Smerilli, A., Caramanti, M., Morgese, F., Torniai, M., Savini, A., and Fiordoliva, I. (2016). Risk of Hyponatraemia in Cancer Patients Treated with Targeted Therapies: A Systematic Review and Meta-Analysis of Clinical Trials. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152079"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"922","DOI":"10.2215\/CJN.14671121","article-title":"Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy","volume":"17","author":"Uppal","year":"2022","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_9","first-page":"1678","article-title":"The Incidence of Hyponatraemia and Its Effect on the ECOG Performance Status among Lung Cancer Patients","volume":"7","author":"Sengupta","year":"2013","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1758835919877725","DOI":"10.1177\/1758835919877725","article-title":"Syndrome of inappropriate anti-diuretic hormone secretion in cancer patients: Results of the first multicenter Italian study","volume":"11","author":"Berardi","year":"2019","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1001\/archinternmed.2009.513","article-title":"Impact of hospital-associated hyponatremia on selected outcomes","volume":"170","author":"Wald","year":"2010","journal-title":"Arch. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1007\/s00520-015-2683-z","article-title":"Hyponatremia is a predictor of hospital length and cost of stay and outcome in cancer patients","volume":"23","author":"Berardi","year":"2015","journal-title":"Support. Care Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.lungcan.2009.05.015","article-title":"The occurrence of hyponatremia in SCLC and the influence on prognosis: A retrospective study of 453 patients treated in a single institution in a 10-year period","volume":"68","author":"Hansen","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12993","DOI":"10.1038\/s41598-019-49601-3","article-title":"Weighing the prognostic role of hyponatremia in hospitalized patients with metastatic solid tumors: The HYPNOSIS study","volume":"9","author":"Mariani","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Corona, G., Giuliani, C., Parenti, G., Norello, D., Verbalis, J.G., Forti, G., Maggi, M., and Peri, A. (2013). Moderate hyponatremia is associated with increased risk of mortality: Evidence from a meta-analysis. PLoS ONE, 8.","DOI":"10.1530\/endoabs.32.P864"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1530\/EJE-15-0111","article-title":"Hyponatremia and mortality risk: A Danish cohort study of 279,508 acutely hospitalized patients","volume":"173","author":"Christiansen","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Corona, G., Giuliani, C., Verbalis, J.G., Forti, G., Maggi, M., and Peri, A. (2015). Hyponatremia improvement is associated with a reduced risk of mortality: Evidence from a meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124105"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Balachandran, K., Okines, A., Gunapala, R., Morganstein, D., and Popat, S. (2015). Resolution of severe hyponatraemia is associated with improved survival in patients with cancer. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1156-6"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.mehy.2012.05.023","article-title":"Proposing the use of hyponatremia as a marker to help identify high risk individuals for lung cancer","volume":"79","author":"Kasi","year":"2012","journal-title":"Med. Hypotheses"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s12020-019-02135-0","article-title":"Effects of low extracellular sodium on proliferation and invasive activity of cancer cells in vitro","volume":"67","author":"Marroncini","year":"2020","journal-title":"Endocrine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s40618-022-01962-9","article-title":"Hyponatremia-related liver steatofibrosis and impaired spermatogenesis: Evidence from a mouse model of the syndrome of inappropriate antidiuresis","volume":"46","author":"Marroncini","year":"2023","journal-title":"J. Endocrinol. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"111419","DOI":"10.1016\/j.mce.2021.111419","article-title":"Low sodium and tolvaptan have opposite effects in human small cell lung cancer cells","volume":"537","author":"Marroncini","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Marroncini, G., Naldi, L., Fibbi, B., Errico, A., Polvani, S., Brogi, M., Fanelli, A., Maggi, M., and Peri, A. (2023). Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202310.0905.v1"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fibbi, B., Marroncini, G., Anceschi, C., Naldi, L., and Peri, A. (2021). Hyponatremia and Oxidative Stress. Antioxidants, 10.","DOI":"10.3390\/antiox10111768"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1080\/0284186X.2018.1477256","article-title":"Hyponatremia associates with poor outcome in metastatic renal cell carcinoma patients treated with everolimus: Prognostic impact","volume":"57","author":"Bono","year":"2018","journal-title":"Acta Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1111\/j.1442-2042.2012.03115.x","article-title":"Impact of hyponatremia on survival of patients with metastatic renal cell carcinoma treated with molecular targeted therapy","volume":"19","author":"Kawashima","year":"2012","journal-title":"Int. J. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/sj.bjc.6605563","article-title":"Hyponatremia as a prognostic and predictive factor in metastatic renal cell carcinoma","volume":"102","author":"Jeppesen","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23871","DOI":"10.18632\/oncotarget.13372","article-title":"Hyponatremia normalization as an independent prognostic factor in patients with advanced non-small cell lung cancer treated with first-line therapy","volume":"8","author":"Berardi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.4103\/0973-1482.187296","article-title":"Prognostic significance of pretreatment sodium levels in patients of nonsmall cell lung cancer treated with pemetrexed-platinum doublet chemotherapy","volume":"14","author":"Doshi","year":"2018","journal-title":"J. Cancer Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s11523-018-0599-5","article-title":"Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy","volume":"13","author":"Galli","year":"2018","journal-title":"Target. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1007\/s10620-020-06380-6","article-title":"Lower Serum Sodium Levels Are Associated with the Therapeutic Effect of Sorafenib on Hepatocellular Carcinoma","volume":"66","author":"Kegasawa","year":"2021","journal-title":"Dig. Dis. Sci."},{"key":"ref_32","first-page":"7461","article-title":"Predictive and prognostic significance of sodium levels in patients with NSCLC treated by erlotinib","volume":"34","author":"Svaton","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41419-019-2081-4","article-title":"Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells","volume":"10","author":"Kleih","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nrc.2017.53","article-title":"Targeting autophagy in cancer","volume":"17","author":"Levy","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.canlet.2020.06.015","article-title":"Autophagy in the crosstalk between tumor and microenvironment","volume":"490","author":"Camuzard","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40880-017-0219-2","article-title":"Autophagy and multidrug resistance in cancer","volume":"36","author":"Li","year":"2017","journal-title":"Chin. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"K\u00f6berle, B., and Schoch, S. (2021). Platinum Complexes in Colorectal Cancer and Other Solid Tumors. Cancers, 13.","DOI":"10.3390\/cancers13092073"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1002\/cbin.11359","article-title":"New insights into small-cell lung cancer development and therapy","volume":"44","author":"Wang","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1097\/SMJ.0b013e3181e63682","article-title":"Cisplatin-induced renal salt wasting syndrome","volume":"103","author":"Hamdi","year":"2010","journal-title":"South Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.eucr.2017.02.001","article-title":"Syndrome of Inappropriate Secretion of Antidiuretic Hormone Caused by Carboplatin after Switching from Cisplatin in a Metastatic Urethral Cancer Patient","volume":"12","author":"Sugiyama","year":"2017","journal-title":"Urol. Case Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Castillo, J.J., Glezerman, I.G., Boklage, S.H., Chiodo, J., Tidwell, B.A., Lamerato, L.E., and Schulman, K.L. (2016). The occurrence of hyponatremia and its importance as a prognostic factor in a cross-section of cancer patients. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2610-9"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.7150\/thno.69424","article-title":"Platinum-based drugs for cancer therapy and anti-tumor strategies","volume":"12","author":"Zhang","year":"2022","journal-title":"Theranostics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1039\/c2mt20058a","article-title":"Platinum(II\/IV) complexes containing ethylenediamine-N,N\u2032-di-2\/3-propionate ester ligands induced caspase-dependent apoptosis in cisplatin-resistant colon cancer cells","volume":"4","author":"Zmejkovski","year":"2012","journal-title":"Metallomics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/14737140.2017.1285230","article-title":"Overview and recent advances in the treatment of neuroblastoma","volume":"17","author":"Whittle","year":"2017","journal-title":"Expert Rev. Anticancer. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1113\/EP085806","article-title":"Hyponatraemia alters the biophysical properties of neuronal cells independently of osmolarity: A study on Ni(2+) -sensitive current involvement","volume":"101","author":"Squecco","year":"2016","journal-title":"Exp. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Patergnani, S., Danese, A., Bouhamida, E., Aguiari, G., Previati, M., Pinton, P., and Giorgi, C. (2020). Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218323"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12032-023-02237-w","article-title":"Moving beyond cisplatin resistance: Mechanisms, challenges, and prospects for overcoming recurrence in clinical cancer therapy","volume":"41","author":"Fu","year":"2023","journal-title":"Med. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1111\/cas.15770","article-title":"ELF1 suppresses autophagy to reduce cisplatin resistance via the miR-152-3p\/NCAM1\/ERK axis in lung cancer cells","volume":"114","author":"Zhao","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/s41419-019-1660-8","article-title":"Knockdown of TRIM65 inhibits autophagy and cisplatin resistance in A549\/DDP cells by regulating miR-138-5p\/ATG7","volume":"10","author":"Pan","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2018.12.005","article-title":"Long-term effects after treatment with platinum compounds, cisplatin and [Pt(O,O\u2032-acac)(\u03b3-acac)(DMS)]: Autophagy activation in rat B50 neuroblastoma cells","volume":"364","author":"Grimaldi","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_51","first-page":"3805","article-title":"LncRNA SNHG7 enhances chemoresistance in neuroblastoma through cisplatin-induced autophagy by regulating miR-329-3p\/MYO10 axis","volume":"24","author":"Wang","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cbi.2018.10.014","article-title":"Knockdown of galectin-1 facilitated cisplatin sensitivity by inhibiting autophagy in neuroblastoma cells","volume":"297","author":"Gao","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Han, Y., Zhou, S., Wang, X., Mao, E., and Huang, L. (2020). SNHG14 stimulates cell autophagy to facilitate cisplatin resistance of colorectal cancer by regulating miR-186\/ATG14 axis. Biomed. Pharmacother., 121.","DOI":"10.1016\/j.biopha.2019.109580"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12943-020-1138-4","article-title":"Autophagy and autophagy-related proteins in cancer","volume":"19","author":"Li","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2174\/156652409788167131","article-title":"Regulation of autophagy through multiple independent hypoxic signaling pathways","volume":"9","author":"Rouschop","year":"2009","journal-title":"Curr. Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/ijc.24402","article-title":"The induction of autophagy by gamma-radiation contributes to the radioresistance of glioma stem cells","volume":"125","author":"Lomonaco","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Vega-Rub\u00edn-de-Celis, S., Kinch, L., and Pe\u00f1a-Llopis, S. (2020). Regulation of Beclin 1-Mediated Autophagy by Oncogenic Tyrosine Kinases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239210"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Tran, S., Fairlie, W.D., and Lee, E.F. (2021). BECLIN1: Protein Structure, Function and Regulation. Cells, 10.","DOI":"10.3390\/cells10061522"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.acr.2017.11.001","article-title":"Bcl-2 Antiapoptotic Family Proteins and Chemoresistance in Cancer","volume":"137","author":"Maji","year":"2018","journal-title":"Adv. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.cell.2009.03.048","article-title":"Autophagy suppresses tumorigenesis through elimination of p62","volume":"137","author":"Mathew","year":"2009","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.phrs.2012.07.004","article-title":"p62\/SQSTM1\/A170: Physiology and pathology","volume":"66","author":"Komatsu","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s12017-013-8235-0","article-title":"Low extracellular sodium causes neuronal distress independently of reduced osmolality in an experimental model of chronic hyponatremia","volume":"15","author":"Benvenuti","year":"2013","journal-title":"Neuromol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s12020-015-0663-1","article-title":"Low extracellular sodium promotes adipogenic commitment of human mesenchymal stromal cells: A novel mechanism for chronic hyponatremia-induced bone loss","volume":"52","author":"Fibbi","year":"2016","journal-title":"Endocrine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s40618-015-0352-1","article-title":"Neuronal distress induced by low extracellular sodium in vitro is partially reverted by the return to normal sodium","volume":"39","author":"Benvenuti","year":"2016","journal-title":"J. Endocrinol. Investig."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:28:33Z","timestamp":1760106513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":64,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084377"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084377","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]}}}