{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:17:44Z","timestamp":1782368264924,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glioblastoma multiforme is the most common and fatal brain tumor among human cancers. Ceramide (Cer) and Sphingosine 1-phosphate (S1P) have emerged as bioeffector molecules that control several biological processes involved in both cancer development and resistance. Cer acts as a tumor suppressor, inhibiting cancer progression, promoting apoptosis, enhancing immunotherapy and sensitizing cells to chemotherapy. In contrast, S1P functions as an onco-promoter molecule, increasing proliferation, survival, invasiveness, and resistance to drug-induced apoptosis. The pro-survival PI3K\/Akt pathway is a recognized downstream target of S1P, and we have previously demonstrated that in glioma cells it also improves Cer transport and metabolism towards complex sphingolipids in glioma cells. Here, we first examined the possibility that, in T98G glioma cells, S1P may regulate Cer metabolism through PI3K\/Akt signaling. Our research showed that exogenous S1P increases the rate of vesicular trafficking of Cer from the endoplasmic reticulum (ER) to the Golgi apparatus through S1P receptor-mediated activation of the PI3K\/Akt pathway. Interestingly, the effect of S1P results in cell protection against toxicity arising from Cer accumulation in the ER, highlighting the role of S1P as a survival factor to escape from the Cer-generating cell death response.<\/jats:p>","DOI":"10.3390\/ijms25158270","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T17:08:34Z","timestamp":1722359314000},"page":"8270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sphingosine 1-Phosphate Stimulates ER to Golgi Ceramide Traffic to Promote Survival in T98G Glioma Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7793-1757","authenticated-orcid":false,"given":"Paola","family":"Giussani","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, LITA Segrate, Via Fratelli Cervi, 93, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana","family":"Brioschi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, LITA Segrate, Via Fratelli Cervi, 93, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enida","family":"Gjoni","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, LITA Segrate, Via Fratelli Cervi, 93, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Riccitelli","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, LITA Segrate, Via Fratelli Cervi, 93, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Viani","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, LITA Segrate, Via Fratelli Cervi, 93, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1586\/14737140.1.3.395","article-title":"Current Epidemiological Trends and Surveillance Issues in Brain Tumors","volume":"1","author":"Davis","year":"2001","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yalamarty, S.S.K., Filipczak, N., Li, X., Subhan, M.A., Parveen, F., Ataide, J.A., Rajmalani, B.A., and Torchilin, V.P. (2023). Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM). Cancers, 15.","DOI":"10.3390\/cancers15072116"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/nrd1380","article-title":"Development of novel targeted therapies in the treatment of malignant glioma","volume":"3","author":"Rich","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1056\/NEJMra0708126","article-title":"Malignant gliomas in adults","volume":"359","author":"Wen","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_5","first-page":"3","article-title":"Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment","volume":"18","author":"Hanif","year":"2017","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4419-6741-1_1","article-title":"An overview of sphingolipid metabolism: From synthesis to breakdown","volume":"688","author":"Gault","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrc1411","article-title":"Biologically active sphingolipids in cancer pathogenesis and treatment","volume":"4","author":"Ogretmen","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.bbalip.2013.12.013","article-title":"Evolving concepts in cancer therapy through targeting sphingolipid metabolism","volume":"1841","author":"Truman","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, R.Z., Wang, X.R., Wang, J., Xie, C., Wang, X.X., Pan, H.D., Meng, W.Y., Liang, T.L., Li, J.X., and Yan, P.Y. (2022). The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.941643"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6488","DOI":"10.1074\/jbc.M409290200","article-title":"CERT mediates intermembrane transfer of various molecular species of ceramides","volume":"280","author":"Kumagai","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41574-020-0320-5","article-title":"The role of ceramides in metabolic disorders: When size and localization matters","volume":"16","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.bbalip.2009.01.006","article-title":"CERT-mediated trafficking of ceramide","volume":"1791","author":"Hanada","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","first-page":"40","article-title":"Ceramide traffic in C6 glioma cells: Evidence for CERT-dependent and independent transport from ER to the Golgi apparatus","volume":"1781","author":"Giussani","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nature02188","article-title":"Molecular machinery for non-vesicular trafficking of ceramide","volume":"426","author":"Hanada","year":"2003","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/978-1-4419-6741-1_2","article-title":"Sphingolipid transport","volume":"688","author":"Riboni","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1002\/1873-3468.13511","article-title":"Structure, functions and regulation of CERT, a lipid-transfer protein for the delivery of ceramide at the ER-Golgi membrane contact sites","volume":"593","author":"Kumagai","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chung, L.H., Liu, D., Liu, X.T., and Qi, Y. (2021). Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413184"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9592","DOI":"10.1074\/jbc.M207729200","article-title":"Ceramide in nitric oxide inhibition of glioma cell growth\u2014Evidence for the involvement of ceramide traffic","volume":"278","author":"Viani","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/j.bbamem.2006.08.012","article-title":"Glycosphingolipids and drug resistance","volume":"1758","author":"Cabot","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1093\/jnci\/91.13.1138","article-title":"Increase of ceramide and induction of mixed apoptosis\/necrosis by N-(4-hydroxyphenyl)- retinamide in neuroblastoma cell lines","volume":"91","author":"Maurer","year":"1999","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s12282-019-00953-8","article-title":"Clinical application of ceramide in cancer treatment","volume":"26","author":"Moro","year":"2019","journal-title":"Breast Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"284","DOI":"10.2174\/157489211796957838","article-title":"Ceramide in chemotherapy of tumors","volume":"6","author":"Rebillard","year":"2011","journal-title":"Recent Pat. Anti-Cancer Drug Discov."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wajapeyee, N., Beamon, T.C., and Gupta, R. (2024). Roles and therapeutic targeting of ceramide metabolism in cancer. Mol. Metab., 83.","DOI":"10.1016\/j.molmet.2024.101936"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/glia.10087","article-title":"Ceramide levels are inversely associated with malignant progression of human glial tumors","volume":"39","author":"Riboni","year":"2002","journal-title":"Glia"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yu, L., He, L., Gan, B., Ti, R., Xiao, Q., Hu, H., Zhu, L., Wang, S., and Ren, R. (2022). Structural insights into sphingosine-1-phosphate receptor activation. Proc. Natl. Acad. Sci. USA, 119.","DOI":"10.1073\/pnas.2117716119"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1194\/jlr.R046300","article-title":"An update on the biology of sphingosine 1-phosphate receptors","volume":"55","author":"Blaho","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104022","DOI":"10.18632\/oncotarget.21955","article-title":"Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/jcb.20097","article-title":"Generation and metabolism of bioactive sphingosine-1-phosphate","volume":"92","author":"Milstien","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-4419-6741-1_10","article-title":"Extracellular and intracellular actions of sphingosine-1-phosphate","volume":"688","author":"Strub","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0304-3835(03)00334-3","article-title":"Sphingosine-1-phosphate stimulates motility and invasiveness of human glioblastoma multiforme cells","volume":"199","author":"Young","year":"2003","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0304-3835(02)00050-2","article-title":"Sphingosine-1-phosphate stimulates human glioma cell proliferation through Gi-coupled receptors: Role of ERK MAP kinase and phosphatidylinositol 3-kinase beta","volume":"181","author":"Letterle","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mahajan-Thakur, S., Bien-Moller, S., Marx, S., Schroeder, H., and Rauch, B.H. (2017). Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112448"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s12935-019-1014-8","article-title":"Roles of sphingosine-1-phosphate signaling in cancer","volume":"19","author":"Wang","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bassi, R., Brambilla, S., Tringali, C., and Giussani, P. (2021). Extracellular Sphingosine-1-Phosphate Downstream of EGFR Increases Human Glioblastoma Cell Survival. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136824"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12935-024-03221-8","article-title":"The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: A promising therapeutic target","volume":"24","author":"Alkafaas","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34541","DOI":"10.1074\/jbc.M301741200","article-title":"Role of human sphingosine-1-phosphate phosphatase 1 in the regulation of intra- and extracellular sphingosine-1-phosphate levels and cell viability","volume":"278","author":"Johnson","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/jnci\/93.5.347","article-title":"Targeting ceramide metabolism\u2014A strategy for overcoming drug resistance","volume":"93","author":"Senchenkov","year":"2001","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Brachtendorf, S., El-Hindi, K., and Gr\u00f6sch, S. (2019). WITHDRAWN: Ceramide synthases in cancer therapy and chemoresistance. Prog. Lipid Res., 74.","DOI":"10.1016\/j.plipres.2019.04.002"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bassi, R., Cas, M.D., Tringali, C., Compostella, F., Paroni, R., and Giussani, P. (2023). Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015394"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1172\/JCI37948","article-title":"Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells","volume":"119","author":"Salazar","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5088","DOI":"10.1074\/jbc.M808934200","article-title":"Phosphatidylinositol 3-Kinase\/AKT Pathway Regulates the Endoplasmic Reticulum to Golgi Traffic of Ceramide in Glioma Cells A link between lipid signaling pathways involved in the control of cell survival","volume":"284","author":"Giussani","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1046\/j.1471-4159.2000.0750503.x","article-title":"Cultured granule cells and astrocytes from cerebellum differ in metabolizing sphingosine","volume":"75","author":"Riboni","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1083\/jcb.113.6.1267","article-title":"A novel fluorescent ceramide analogue for studying membrane traffic in animal cells: Accumulation at the Golgi apparatus results in altered spectral properties of the sphingolipid precursor","volume":"113","author":"Pagano","year":"1991","journal-title":"J. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9078","DOI":"10.1074\/jbc.275.12.9078","article-title":"Serine palmitoyltransferase regulates de novo ceramide generation during etoposide-induced apoptosis","volume":"275","author":"Perry","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"984","DOI":"10.2174\/138955707782110123","article-title":"Sphingolipid signaling pathways as potential therapeutic targets in gliomas","volume":"7","year":"2007","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/glycob\/6.1.33","article-title":"Pathways of glycosphingolipid biosynthesis in SW13 cells in the presence and absence of vimentin intermediate filaments","volume":"6","author":"Gillard","year":"1996","journal-title":"Glycobiology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0300-9084(03)00047-6","article-title":"Salvage pathways in glycosphingolipid metabolism","volume":"85","author":"Tettamanti","year":"2003","journal-title":"Biochimie"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.yexcr.2007.02.009","article-title":"Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness","volume":"313","author":"Young","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1097\/01.jnen.0000175329.59092.2c","article-title":"Sphingosine kinase-1 expression correlates with poor survival of patients with glioblastoma multiforme: Roles of sphingosine kinase isoforms in growth of glioblastoma cell lines","volume":"64","author":"Jackson","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Guan, H., Song, L., Cai, J., Huang, Y., Wu, J., Yuan, J., Li, J., and Li, M. (2011). Sphingosine kinase 1 regulates the Akt\/FOXO3a\/Bim pathway and contributes to apoptosis resistance in glioma cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019946"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1074\/jbc.M601698200","article-title":"Tumor necrosis factor-alpha-stimulated cell proliferation is mediated through sphingosine kinase-dependent Akt activation and cyclin D expression","volume":"282","author":"Seasholtz","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4049\/jimmunol.167.1.173","article-title":"TNF-alpha-induced sphingosine 1-phosphate inhibits apoptosis through a phosphatidylinositol 3-kinase\/Akt pathway in human hepatocytes","volume":"167","author":"Osawa","year":"2001","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gjoni, E., Brioschi, L., Cinque, A., Coant, N., Islam, M.N., Ng, C.K., Verderio, C., Magnan, C., Riboni, L., and Viani, P. (2014). Glucolipotoxicity Impairs Ceramide Flow from the Endoplasmic Reticulum to the Golgi Apparatus in INS-1 beta-Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110875"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5055","DOI":"10.1128\/MCB.02107-05","article-title":"Sphingosine-1-phosphate phosphohydrolase regulates endoplasmic reticulum-to-golgi trafficking of ceramide","volume":"26","author":"Giussani","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_56","first-page":"1100","article-title":"Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival","volume":"8","author":"Ermoian","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1200\/JCO.2004.07.193","article-title":"The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas","volume":"22","author":"Chakravarti","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ccr.2007.04.011","article-title":"Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs","volume":"11","author":"Swanton","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.ccr.2007.05.003","article-title":"A CERTain role for ceramide in taxane-induced cell death","volume":"11","author":"Kolesnick","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-1-4419-6741-1_13","article-title":"Cancer treatment strategies targeting sphingolipid metabolism","volume":"688","author":"Oskouian","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.2217\/fon.10.116","article-title":"Sphingolipids and cancer: Ceramide and sphingosine-1-phosphate in the regulation of cell death and drug resistance","volume":"6","author":"Ponnusamy","year":"2010","journal-title":"Future Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/j.1471-4159.1965.tb04255.x","article-title":"Phospholipids and glycolipids of tumours in the central nervous system","volume":"12","author":"Lou","year":"1965","journal-title":"J. Neurochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3109\/07357907.2011.629379","article-title":"Glucosylceramide synthase protects glioblastoma cells against autophagic and apoptotic death induced by temozolomide and Paclitaxel","volume":"30","author":"Giussani","year":"2012","journal-title":"Cancer Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1042\/bst0311216","article-title":"Exogenous and intracellularly generated sphingosine 1-phosphate can regulate cellular processes by divergent pathways","volume":"31","author":"Spiegel","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s10495-007-0721-0","article-title":"Sphingolipids and cell death","volume":"12","author":"Morales","year":"2007","journal-title":"Apoptosis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/S0076-6879(00)11110-3","article-title":"Estimating sphingolipid metabolism and trafficking in cultured cells using radiolabeled compounds","volume":"311","author":"Riboni","year":"2000","journal-title":"Methods Enzymol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8270\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:25:53Z","timestamp":1760109953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,29]]},"references-count":66,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158270"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158270","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,29]]}}}