{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:35:24Z","timestamp":1792017324588,"version":"4.4.0"},"reference-count":163,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canc\u00e9rop\u00f4le Lyon Auvergne-Rh\u00f4ne-Alpes (CLARA)","award":["CV-2021-027"],"award-info":[{"award-number":["CV-2021-027"]}]},{"name":"Canc\u00e9rop\u00f4le Lyon Auvergne-Rh\u00f4ne-Alpes (CLARA)","award":["5FI14708WOJC"],"award-info":[{"award-number":["5FI14708WOJC"]}]},{"name":"Ligue National Contre le Cancer","award":["CV-2021-027"],"award-info":[{"award-number":["CV-2021-027"]}]},{"name":"Ligue National Contre le Cancer","award":["5FI14708WOJC"],"award-info":[{"award-number":["5FI14708WOJC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Prostate cancer (PC) is the second most common cancer in men worldwide. More than 65% of men diagnosed with PC are above 65. Patients with localized PC show high long-term survival, however with the disease progression into a metastatic form, it becomes incurable, even after strong radio- and\/or chemotherapy. Sphingosine 1-phosphate (S1P) is a bioactive lipid that participates in all the steps of oncogenesis including tumor cell proliferation, survival, migration, invasion, and metastatic spread. The S1P-producing enzymes sphingosine kinases 1 and 2 (SK1 and SK2), and the S1P degrading enzyme S1P lyase (SPL), have been shown to be highly implicated in the onset, development, and therapy resistance of PC during the last 20 years. In this review, the most important studies demonstrating the role of S1P and S1P metabolic partners in PC are discussed. The different in vitro, ex vivo, and in vivo models of PC that were used to demonstrate the implication of S1P metabolism are especially highlighted. Furthermore, the most efficient molecules targeting S1P metabolism that are under preclinical and clinical development for curing PC are summarized. Finally, the possibility of targeting S1P metabolism alone or combined with other therapies in the foreseeable future as an alternative option for PC patients is discussed. Research Strategy: PubMed from INSB was used for article research. First, key words \u201cprostate &amp; sphingosine\u201d were used and 144 articles were found. We also realized other combinations of key words as \u201cprostate cancer bone metastasis\u201d and \u201cprostate cancer treatment\u201d. We used the most recent reviews to illustrate prostate cancer topic and sphingolipid metabolism overview topic.<\/jats:p>","DOI":"10.3390\/cancers15102732","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T09:26:13Z","timestamp":1683883573000},"page":"2732","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Saida","family":"Mebarek","sequence":"first","affiliation":[{"name":"CNRS UMR 5246, INSA Lyon, Institut de Chimie et Biochimie Mol\u00e9culaires et Supramol\u00e9culaires (ICBMS), 69622 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najwa","family":"Skafi","sequence":"additional","affiliation":[{"name":"CNRS, LAGEPP UMR 5007, University of Lyon, Universit\u00e9 Claude Bernard Lyon 1, 43 Bd 11 Novembre 1918, 69622 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyre","family":"Brizuela","sequence":"additional","affiliation":[{"name":"CNRS UMR 5246, INSA Lyon, Institut de Chimie et Biochimie Mol\u00e9culaires et Supramol\u00e9culaires (ICBMS), 69622 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.euo.2021.09.006","article-title":"Epidemiology and Prevention of Prostate Cancer","volume":"4","author":"Gandaglia","year":"2021","journal-title":"Eur. Urol. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s13402-016-0268-6","article-title":"PSA and beyond: Alternative prostate cancer biomarkers","volume":"39","author":"Saini","year":"2016","journal-title":"Cell Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/CCO.0000000000000938","article-title":"Treatments and challenges in advanced prostate cancer","volume":"35","author":"Gourdin","year":"2023","journal-title":"Curr. Opin. Oncol."},{"key":"ref_5","unstructured":"Global Burden of Disease Cancer Collaboration, Fitzmaurice, C., Abate, D., Abbasi, N., Abbastabar, H., Abd-Allah, F., Abdel-Rahman, O., Abdelalim, A., Abdoli, A., and Abdollahpour, I. (2019). Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol., 5, 1749\u20131768."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-020-00243-0","article-title":"Prostate cancer","volume":"7","author":"Rebello","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1200\/JCO.2005.02.9439","article-title":"Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer","volume":"24","author":"Tsuchiya","year":"2006","journal-title":"J Clin. Oncol."},{"key":"ref_8","first-page":"421746","article-title":"Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells","volume":"2015","author":"Sasso","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.molimm.2017.11.023","article-title":"Beyond the vicious cycle: The role of innate osteoimmunity, automimicry and tumor-inherent changes in dictating bone metastasis","volume":"110","author":"Owen","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_10","first-page":"e126333","article-title":"A Multimodal Clinical Approach for the Treatment of Bone Metastases in Solid Tumors","volume":"12","author":"Lanza","year":"2022","journal-title":"Anesth. Pain Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"864980","DOI":"10.3389\/fonc.2022.864980","article-title":"Exosomes Regulate the Epithelial\u2013Mesenchymal Transition in Cancer","volume":"12","author":"Jiang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nrc.2017.6","article-title":"Pre-metastatic niches: Organ-specific homes for metastases","volume":"17","author":"Peinado","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.canlet.2022.01.015","article-title":"Tumor microenvironment mechanisms and bone metastatic disease progression of prostate cancer","volume":"530","author":"Kang","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Baldessari, C., Pipitone, S., Molinaro, E., Cerma, K., Fanelli, M., Nasso, C., Oltrecolli, M., Pirola, M., D\u2019Agostino, E., and Pugliese, G. (2023). Bone Metastases and Health in Prostate Cancer: From Pathophysiology to Clinical Implications. Cancers, 15.","DOI":"10.3390\/cancers15051518"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e10126","DOI":"10.1002\/jbm4.10126","article-title":"Bone as a Preferential Site for Metastasis","volume":"3","author":"Sowder","year":"2019","journal-title":"JBMR Plus"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kan, C., Vargas, G., Pape, F.L., and Cl\u00e9zardin, P. (2016). Cancer Cell Colonisation in the Bone Microenvironment. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101674"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/biosci\/biv084","article-title":"Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study","volume":"65","author":"Zaborowski","year":"2015","journal-title":"Bioscience"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"94834","DOI":"10.18632\/oncotarget.22014","article-title":"Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic metastasis of prostate cancer","volume":"8","author":"Ye","year":"2017","journal-title":"Oncotarget"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5369","DOI":"10.2147\/IJGM.S361981","article-title":"Exosome-Derived miRNAs as Potential Biomarkers for Prostate Bone Metastasis","volume":"15","author":"Lu","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Akoto, T., and Saini, S. (2021). Role of Exosomes in Prostate Cancer Metastasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073528"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/s41585-019-0237-8","article-title":"Towards precision oncology in advanced prostate cancer","volume":"16","author":"Ku","year":"2019","journal-title":"Nat. Rev. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"903","DOI":"10.2217\/imt-2019-0019","article-title":"The evolving landscape of immunotherapy in advanced prostate cancer","volume":"11","author":"Patel","year":"2019","journal-title":"Immunotherapy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrc4016","article-title":"Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer","volume":"15","author":"Watson","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/17512433.2023.2181783","article-title":"Prostate cancer and novel pharmacological treatment options-what\u2019s new for 2022?","volume":"16","author":"Marchetti","year":"2023","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.5534\/wjmh.220200","article-title":"Systemic Therapies for Metastatic Castration-Resistant Prostate Cancer: An Updated Review","volume":"41","author":"Hatano","year":"2023","journal-title":"World J. Mens. Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114392","DOI":"10.1016\/j.biopha.2023.114392","article-title":"Paclitaxel and docetaxel resistance in prostate cancer: Molecular mechanisms and possible therapeutic strategies","volume":"160","author":"Hashemi","year":"2023","journal-title":"Biomed. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rastogi, I., Muralidhar, A., and McNeel, D.G. (2023). Vaccines as treatments for prostate cancer. Nat. Rev. Urol., 1\u201316.","DOI":"10.1038\/s41585-023-00739-w"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3109\/10409238.2015.1039115","article-title":"Sphingosine-1-phosphate metabolism: A structural perspective","volume":"50","author":"Donaldson","year":"2015","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"745092","DOI":"10.3389\/fonc.2021.745092","article-title":"Targeting Sphingolipids for Cancer Therapy","volume":"11","author":"Companioni","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1172\/JCI77685","article-title":"Erythrocyte-derived sphingosine 1-phosphate is essential for vascular development","volume":"124","author":"Xiong","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.bbalip.2012.06.002","article-title":"Sphingosine-1-phosphate signaling controlling osteoclasts and bone homeostasis","volume":"1831","author":"Ishii","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1172\/JCI30674","article-title":"Maternal disturbance in activated sphingolipid metabolism causes pregnancy loss in mice","volume":"117","author":"Mizugishi","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cmet.2021.06.006","article-title":"Sphingolipids in metabolic disease: The good, the bad, and the unknown","volume":"33","author":"Green","year":"2021","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"Hannun","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108381","DOI":"10.1016\/j.pharmthera.2023.108381","article-title":"The role of sphingosine 1-phosphate metabolism in brain health and disease","volume":"244","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.plipres.2016.03.001","article-title":"Sphingosine 1-phosphate and sphingosine kinases in health and disease: Recent advances","volume":"62","author":"Pyne","year":"2016","journal-title":"Prog. Lipid. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3389\/fncel.2014.00283","article-title":"Fingolimod for the treatment of neurological diseases-state of play and future perspectives","volume":"8","author":"Brunkhorst","year":"2014","journal-title":"Front. Cell Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1111\/cas.13802","article-title":"The role of sphingosine-1-phosphate in inflammation and cancer progression","volume":"109","author":"Nagahashi","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.cellsig.2013.01.002","article-title":"The roles of sphingosine kinases 1 and 2 in regulating the Warburg effect in prostate cancer cells","volume":"25","author":"Watson","year":"2013","journal-title":"Cell Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16394","DOI":"10.1073\/pnas.0603734103","article-title":"Role of ABCC1 in export of sphingosine-1-phosphate from mast cells","volume":"103","author":"Mitra","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10477","DOI":"10.1074\/jbc.M109.064162","article-title":"Estradiol induces export of sphingosine 1-phosphate from breast cancer cells via ABCC1 and ABCG2","volume":"285","author":"Takabe","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1126\/science.1167449","article-title":"The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors","volume":"323","author":"Kawahara","year":"2009","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1002\/jcb.22507","article-title":"Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1-phosphate","volume":"109","author":"Bode","year":"2010","journal-title":"J. Cell Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Nakajima, M., Nagahashi, M., Rashid, O.M., Takabe, K., and Wakai, T. (2017). The role of sphingosine-1-phosphate in the tumor microenvironment and its clinical implications. Tumour. Biol., 39.","DOI":"10.1177\/1010428317699133"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4330\/wjc.v5.i4.75","article-title":"Sphingolipids in cardiovascular and cerebrovascular systems: Pathological implications and potential therapeutic targets","volume":"5","author":"Kawabori","year":"2013","journal-title":"World J. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6850","DOI":"10.1523\/JNEUROSCI.6467-10.2011","article-title":"BACE1 activity is modulated by cell-associated sphingosine-1-phosphate","volume":"31","author":"Takasugi","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1096\/fj.14-261289","article-title":"Sphingosine 1-phosphate is a ligand for peroxisome proliferator-activated receptor-\u03b3 that regulates neoangiogenesis","volume":"29","author":"Parham","year":"2015","journal-title":"FASEB J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1096\/fj.10-167502","article-title":"Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration","volume":"25","author":"Strub","year":"2011","journal-title":"FASEB J."},{"key":"ref_51","first-page":"ra58","article-title":"Binding of the sphingolipid S1P to hTERT stabilizes telomerase at the nuclear periphery by allosterically mimicking protein phosphorylation","volume":"8","author":"Oaks","year":"2015","journal-title":"Sci. Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.1176709","article-title":"Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate","volume":"325","author":"Hait","year":"2009","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1124\/pr.107.07113","article-title":"\u201cInside-out\u201d signaling of sphingosine-1-phosphate: Therapeutic targets","volume":"60","author":"Takabe","year":"2008","journal-title":"Pharmacol. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/381800a0","article-title":"Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate","volume":"381","author":"Cuvillier","year":"1996","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0014-5793(97)00304-9","article-title":"Sphingosine induces apoptosis in androgen-independent human prostatic carcinoma DU-145 cells by suppression of bcl-X(L) gene expression","volume":"407","author":"Shirahama","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1006\/excr.1997.3653","article-title":"Regulation of lipid signaling pathways for cell survival and apoptosis by bcl-2 in prostate carcinoma cells","volume":"234","author":"Herrmann","year":"1997","journal-title":"Exp. Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1442-2042.2006.01249.x","article-title":"Importance of C16 ceramide accumulation during apoptosis in prostate cancer cells","volume":"13","author":"Eto","year":"2006","journal-title":"Int. J. Urol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1002\/pros.20645","article-title":"Sphingolipids and the sphingosine kinase inhibitor, SKI II, induce BCL-2-independent apoptosis in human prostatic adenocarcinoma cells","volume":"67","author":"Leroux","year":"2007","journal-title":"Prostate"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11667","DOI":"10.1158\/0008-5472.CAN-05-2702","article-title":"Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models","volume":"65","author":"Pchejetski","year":"2005","journal-title":"Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"759","DOI":"10.7164\/antibiotics.53.759","article-title":"Characterization of B-5354c, a new sphingosine kinase inhibitor, produced by a marine bacterium","volume":"53","author":"Kono","year":"2000","journal-title":"J. Antibiot."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1158\/1535-7163.MCT-07-2322","article-title":"Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models","volume":"7","author":"Pchejetski","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/(SICI)1097-0045(19990615)40:1<50::AID-PROS6>3.0.CO;2-N","article-title":"Early induction of apoptosis in androgen-independent prostate cancer cell line by FTY720 requires caspase-3 activation","volume":"40","author":"Wang","year":"1999","journal-title":"Prostate"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/ijc.10178","article-title":"Anticarcinogenic effect of FTY720 in human prostate carcinoma DU145 cells: Modulation of mitogenic signaling, FAK, cell-cycle entry and apoptosis","volume":"98","author":"Permpongkosol","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8651","DOI":"10.1158\/0008-5472.CAN-10-1388","article-title":"FTY720 (fingolimod) sensitizes prostate cancer cells to radiotherapy by inhibition of sphingosine kinase-1","volume":"70","author":"Pchejetski","year":"2010","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"76995","DOI":"10.18632\/oncotarget.12765","article-title":"Non-immunosuppressive triazole-based small molecule induces anticancer activity against human hormone-refractory prostate cancers: The role in inhibition of PI3K\/AKT\/mTOR and c-Myc signaling pathways","volume":"7","author":"Leu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.bbrc.2006.02.070","article-title":"High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation","volume":"342","author":"Akao","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1002\/pros.20994","article-title":"Signal transduction responses to lysophosphatidic acid and sphingosine 1-phosphate in human prostate cancer cells: Responses to LPA and S1P in Human Prostate Cancer Cells","volume":"69","author":"Gibbs","year":"2009","journal-title":"Prostate"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"eaah4007","DOI":"10.1126\/scisignal.aah4007","article-title":"Sphingosine 1-phosphate signaling through its receptor S1P5 promotes chromosome segregation and mitotic progression","volume":"10","author":"Andrieu","year":"2017","journal-title":"Sci. Signal"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"C451","DOI":"10.1152\/ajpcell.00586.2008","article-title":"S1P 5 is required for sphingosine 1-phosphate-induced autophagy in human prostate cancer PC-3 cells","volume":"297","author":"Chang","year":"2009","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.cellsig.2013.11.024","article-title":"Extrinsic sphingosine 1-phosphate activates S1P5 and induces autophagy through generating endoplasmic reticulum stress in human prostate cancer PC-3 cells","volume":"26","author":"Huang","year":"2014","journal-title":"Cell Signal."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Almatroudi, A., Khan, A.A., Alhumaydhi, F.A., Alsahli, M.A., and Rahmani, A.H. (2020). Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer. Molecules, 25.","DOI":"10.3390\/molecules25143146"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"644134","DOI":"10.3389\/fonc.2021.644134","article-title":"Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors","volume":"11","author":"Guo","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1011435","DOI":"10.3389\/fcell.2022.1011435","article-title":"Modern aspects of the use of natural polyphenols in tumor prevention and therapy","volume":"10","author":"Sufianova","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.1096\/fj.10-160838","article-title":"The sphingosine kinase-1 survival pathway is a molecular target for the tumor-suppressive tea and wine polyphenols in prostate cancer","volume":"24","author":"Brizuela","year":"2010","journal-title":"FASEB J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.pharep.2013.08.014","article-title":"Inhibition of sphingosine kinase-2 ablates androgen resistant prostate cancer proliferation and survival","volume":"66","author":"Gestaut","year":"2014","journal-title":"Pharmacol. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1158\/1541-7786.MCR-14-0626","article-title":"Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression","volume":"13","author":"Schrecengost","year":"2015","journal-title":"Mol. Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1158\/1535-7163.MCT-15-0279","article-title":"The Sphingosine Kinase 2 Inhibitor ABC294640 Reduces the Growth of Prostate Cancer Cells and Results in Accumulation of Dihydroceramides In Vitro and In Vivo","volume":"14","author":"Venant","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.toxlet.2018.04.008","article-title":"Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid metabolism within prostate cancer cells","volume":"291","author":"Allam","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/ijc.21243","article-title":"FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer","volume":"117","author":"Chua","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.3390\/md13063276","article-title":"Activation of the Tumor Suppressor PP2A Emerges as a Potential Therapeutic Strategy for Treating Prostate Cancer","volume":"13","author":"Daoud","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.canlet.2005.02.039","article-title":"FTY720, a fungus metabolite, inhibits invasion ability of androgen-independent prostate cancer cells through inactivation of RhoA-GTPase","volume":"233","author":"Zhou","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_82","first-page":"3042","article-title":"CWR22: The first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivo and in soft agar","volume":"56","author":"Nagabhushan","year":"1996","journal-title":"Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Dayon, A., Brizuela, L., Martin, C., Mazerolles, C., Pirot, N., Doumerc, N., Nogueira, L., Golzio, M., Teissi\u00e9, J., and Serre, G. (2009). Sphingosine kinase-1 is central to androgen-regulated prostate cancer growth and survival. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008048"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1111\/bph.12035","article-title":"The sphingosine kinase inhibitor 2-(p-hyroxyanilino)-4-(p-chlorophenyl)thiazole reduces androgen receptor expression via an oxidative stress-dependent mechanism","volume":"168","author":"Tonelli","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"103625","DOI":"10.1016\/j.ebiom.2021.103625","article-title":"Overcoming enzalutamide resistance in metastatic prostate cancer by targeting sphingosine kinase","volume":"72","author":"Lin","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e695","DOI":"10.1002\/ctm2.695","article-title":"The central role of Sphingosine kinase 1 in the development of neuroendocrine prostate cancer (NEPC): A new targeted therapy of NEPC","volume":"12","author":"Lee","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8635","DOI":"10.1158\/0008-5472.CAN-08-0917","article-title":"Sphingosine Kinase 1: A New Modulator of Hypoxia Inducible Factor 1\u03b1 during Hypoxia in Human Cancer Cells","volume":"68","author":"Ader","year":"2008","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1074\/jbc.M708241200","article-title":"Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells. Role of hypoxia-inducible factors 1 and 2","volume":"283","author":"Anelli","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e209","DOI":"10.1038\/oncsis.2016.13","article-title":"Essential role for SphK1\/S1P signaling to regulate hypoxia-inducible factor 2\u03b1 expression and activity in cancer","volume":"5","author":"Bouquerel","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1600-079X.2011.00865.x","article-title":"Sphingosine kinase 1 pathway is involved in melatonin-induced HIF-1\u03b1 inactivation in hypoxic PC-3 prostate cancer cells","volume":"51","author":"Cho","year":"2011","journal-title":"J. Pineal. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1016\/j.bmcl.2014.03.084","article-title":"Coumestrol suppresses hypoxia inducible factor 1\u03b1 by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells","volume":"24","author":"Cho","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Lee, S.-O., Kim, J.-S., Lee, M.-S., and Lee, H.-J. (2016). Anti-cancer effect of pristimerin by inhibition of HIF-1\u03b1 involves the SPHK-1 pathway in hypoxic prostate cancer cells. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2730-2"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Lee, M.-S., Lee, S.-O., Kim, K.-R., and Lee, H.-J. (2017). Sphingosine Kinase-1 Involves the Inhibitory Action of HIF-1\u03b1 by Chlorogenic Acid in Hypoxic DU145 Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020325"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"13803","DOI":"10.18632\/oncotarget.3144","article-title":"Neutralizing S1P inhibits intratumoral hypoxia, induces vascular remodelling and sensitizes to chemotherapy in prostate cancer","volume":"6","author":"Ader","year":"2015","journal-title":"Oncotarget"},{"key":"ref_95","first-page":"4468","article-title":"Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells","volume":"60","author":"Nava","year":"2000","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/sj.cdd.4401145","article-title":"Role of ceramide in mediating apoptosis of irradiated LNCaP prostate cancer cells","volume":"10","author":"Kimura","year":"2003","journal-title":"Cell Death Differ."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1158\/1535-7163.MCT-12-0227","article-title":"First evidence of sphingosine 1-phosphate lyase protein expression and activity downregulation in human neoplasm: Implication for resistance to therapeutics in prostate cancer","volume":"11","author":"Brizuela","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1002\/ijc.24640","article-title":"Sphingosine kinase 1 inhibition sensitizes hormone-resistant prostate cancer to docetaxel","volume":"125","author":"Sauer","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.bbrc.2017.03.084","article-title":"Modulation of the sphingolipid rheostat is involved in paclitaxel resistance of the human prostate cancer cell line PC3-PR","volume":"486","author":"Aoyama","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/emmm.201200244","article-title":"Communication between host organism and cancer cells is transduced by systemic sphingosine kinase 1\/sphingosine 1-phosphate signalling to regulate tumour metastasis","volume":"4","author":"Ponnusamy","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"115087","DOI":"10.1016\/j.bone.2019.115087","article-title":"The role of sphingosine 1-phosphate metabolism in bone and joint pathologies and ectopic calcification","volume":"130","author":"Bougault","year":"2020","journal-title":"Bone"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4322","DOI":"10.1158\/1078-0432.CCR-08-3157","article-title":"Suppression of androgen-independent prostate cancer cell aggressiveness by FTY720: Validating Runx2 as a potential antimetastatic drug screening platform","volume":"15","author":"Chua","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.molonc.2014.04.001","article-title":"Osteoblast-derived sphingosine 1-phosphate to induce proliferation and confer resistance to therapeutics to bone metastasis-derived prostate cancer cells","volume":"8","author":"Brizuela","year":"2014","journal-title":"Mol. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5580","DOI":"10.1038\/s41388-019-0833-3","article-title":"Activation of sphingosine kinase by lipopolysaccharide promotes prostate cancer cell invasion and metastasis via SphK1\/S1PR4\/matriptase","volume":"38","author":"Lee","year":"2019","journal-title":"Oncogene"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Fujita, K., Matsushita, M., De Velasco, M.A., Hatano, K., Minami, T., Nonomura, N., and Uemura, H. (2023). The Gut-Prostate Axis: A New Perspective of Prostate Cancer Biology through the Gut Microbiome. Cancers, 15.","DOI":"10.3390\/cancers15051375"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1016\/j.ejca.2010.07.053","article-title":"Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens","volume":"46","author":"Malavaud","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2250407","DOI":"10.1155\/2022\/2250407","article-title":"Expression Profile of Sphingosine Kinase 1 Isoforms in Human Cancer Tissues and Cells: Importance and Clinical Relevance of the Neglected 1b-Isoform","volume":"2022","author":"Chen","year":"2022","journal-title":"J. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/bjc.2012.14","article-title":"Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection","volume":"106","author":"Nunes","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"100201","DOI":"10.1074\/jbc.RA120.012941","article-title":"Erythrocytes efficiently utilize exogenous sphingosines for S1P synthesis and export via Mfsd2b","volume":"296","author":"Nguyen","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1258\/acb.2007.007189","article-title":"Plasma sphingosine-1-phosphate measurement in healthy subjects: Close correlation with red blood cell parameters","volume":"45","author":"Ohkawa","year":"2008","journal-title":"Ann. Clin. Biochem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1074\/mcp.M115.052381","article-title":"Integration of Metabolomics and Transcriptomics Reveals Major Metabolic Pathways and Potential Biomarker Involved in Prostate Cancer","volume":"15","author":"Ren","year":"2016","journal-title":"Mol. Cell Proteom."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41419-022-05064-5","article-title":"The crosstalk between endothelial cells and vascular smooth muscle cells aggravates high phosphorus-induced arterial calcification","volume":"13","author":"Lin","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"730638","DOI":"10.3389\/fonc.2021.730638","article-title":"Metabolomics Profiling Discriminates Prostate Cancer From Benign Prostatic Hyperplasia Within the Prostate-Specific Antigen Gray Zone","volume":"11","author":"Xu","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"12892","DOI":"10.1021\/bi980744d","article-title":"N,N-Dimethylsphingosine is a potent competitive inhibitor of sphingosine kinase but not of protein kinase C: Modulation of cellular levels of sphingosine 1-phosphate and ceramide","volume":"37","author":"Edsall","year":"1998","journal-title":"Biochemistry"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1021\/bi9515533","article-title":"N,N-dimethylsphingosine inhibition of sphingosine kinase and sphingosine 1-phosphate activity in human platelets","volume":"35","author":"Yatomi","year":"1996","journal-title":"Biochemistry"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/(SICI)1097-0215(19960503)66:3<358::AID-IJC16>3.0.CO;2-7","article-title":"Sphingosine and its methylated derivative N,N-dimethylsphingosine (DMS) induce apoptosis in a variety of human cancer cell lines","volume":"66","author":"Sweeney","year":"1996","journal-title":"Int. J. Cancer"},{"key":"ref_117","first-page":"1613","article-title":"Cell membrane signaling as target in cancer therapy: Inhibitory effect of N,N-dimethyl and N,N,N-trimethyl sphingosine derivatives on in vitro and in vivo growth of human tumor cells in nude mice","volume":"51","author":"Endo","year":"1991","journal-title":"Cancer Res."},{"key":"ref_118","first-page":"257","article-title":"In vitro and in vivo induction of apoptosis by sphingosine and N, N-dimethylsphingosine in human epidermoid carcinoma KB-3-1 and its multidrug-resistant cells","volume":"3","author":"Shirahama","year":"1997","journal-title":"Clin. Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.1016\/S0021-9258(19)50708-6","article-title":"Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways","volume":"267","author":"Buehrer","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1093\/jnci\/92.23.1897","article-title":"Synergistic cytotoxicity in solid tumor cell lines between N-(4-hydroxyphenyl)retinamide and modulators of ceramide metabolism","volume":"92","author":"Maurer","year":"2000","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/00005392-199707000-00084","article-title":"Protein kinase C mediated anti-proliferative glucocorticoid-sphinganine synergism in cultured Pollard III prostate tumor cells","volume":"158","author":"Sosnowski","year":"1997","journal-title":"J. Urol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/01480540701375018","article-title":"Safingol toxicology after oral administration to TRAMP mice: Demonstration of safingol uptake and metabolism by N-acylation and N-methylation","volume":"30","author":"Morales","year":"2007","journal-title":"Drug Chem. Toxicol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1093\/jnci\/87.18.1394","article-title":"Potentiation of apoptosis by treatment with the protein kinase C-specific inhibitor safingol in mitomycin C-treated gastric cancer cells","volume":"87","author":"Schwartz","year":"1995","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_124","first-page":"1463","article-title":"The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells","volume":"35","author":"Ling","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_125","first-page":"905","article-title":"Role of reactive oxygen species in the synergistic cytotoxicity of safingol-based combination regimens with conventional chemotherapeutics","volume":"2","author":"Ling","year":"2011","journal-title":"Oncol. Lett."},{"key":"ref_126","first-page":"537","article-title":"A pilot clinical\/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin","volume":"3","author":"Schwartz","year":"1997","journal-title":"Clin. Cancer Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1158\/1078-0432.CCR-10-2323","article-title":"A phase I clinical trial of safingol in combination with cisplatin in advanced solid tumors","volume":"17","author":"Dickson","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Matula, K., Collie-Duguid, E., Murray, G., Parikh, K., Grabsch, H., Tan, P., Lalwani, S., Garau, R., Ong, Y., and Bain, G. (2015). Regulation of cellular sphingosine-1-phosphate by sphingosine kinase 1 and sphingosine-1-phopshate lyase determines chemotherapy resistance in gastroesophageal cancer. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1718-7"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"19060","DOI":"10.1074\/jbc.273.30.19060","article-title":"Acylation of naturally occurring and synthetic 1-deoxysphinganines by ceramide synthase. Formation of N-palmitoyl-aminopentol produces a toxic metabolite of hydrolyzed fumonisin, AP1, and a new category of ceramide synthase inhibitor","volume":"273","author":"Humpf","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1021\/ml2000164","article-title":"Novel synthesis and biological evaluation of enigmols as therapeutic agents for treating prostate cancer","volume":"2","author":"Mays","year":"2011","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1158\/1535-7163.MCT-10-0754","article-title":"Enigmol: A novel sphingolipid analogue with anticancer activity against cancer cell lines and in vivo models for intestinal and prostate cancer","volume":"10","author":"Symolon","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S1043-6618(03)00054-9","article-title":"Sphingoid bases and de novo ceramide synthesis: Enzymes involved, pharmacology and mechanisms of action","volume":"47","author":"Menaldino","year":"2003","journal-title":"Pharmacol. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1021\/acsmedchemlett.6b00113","article-title":"Discovery of a Fluorinated Enigmol Analog with Enhanced in Vivo Pharmacokinetic and Anti-Tumor Properties","volume":"7","author":"Miller","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_134","first-page":"5962","article-title":"Discovery and evaluation of inhibitors of human sphingosine kinase","volume":"63","author":"French","year":"2003","journal-title":"Cancer Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1124\/jpet.106.101345","article-title":"Antitumor activity of sphingosine kinase inhibitors","volume":"318","author":"French","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.7150\/ijbs.71381","article-title":"The sphingosine kinase inhibitor SKI-V suppresses cervical cancer cell growth","volume":"18","author":"Zhang","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"38841","DOI":"10.1074\/jbc.M110.127993","article-title":"The sphingosine kinase 1 inhibitor 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole induces proteasomal degradation of sphingosine kinase 1 in mammalian cells","volume":"285","author":"Loveridge","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"16663","DOI":"10.18632\/oncotarget.7693","article-title":"Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKI or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells","volume":"7","author":"McNaughton","year":"2016","journal-title":"Oncotarget"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1124\/jpet.109.163444","article-title":"Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2","volume":"333","author":"French","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1124\/jpet.109.163337","article-title":"A novel sphingosine kinase inhibitor induces autophagy in tumor cells","volume":"333","author":"Beljanski","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1158\/1078-0432.CCR-16-2363","article-title":"A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors","volume":"23","author":"Britten","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00277-022-05056-7","article-title":"Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and\/or refractory multiple myeloma","volume":"102","author":"Kang","year":"2023","journal-title":"Ann. Hematol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1056\/NEJMoa0907839","article-title":"Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis","volume":"362","author":"Cohen","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJMoa0909494","article-title":"A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis","volume":"362","author":"Kappos","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1056\/NEJMoa1800149","article-title":"Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis","volume":"379","author":"Chitnis","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"36865","DOI":"10.1074\/jbc.M506293200","article-title":"Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720","volume":"280","author":"Kharel","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1096\/fj.03-0910fje","article-title":"The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein-coupled receptors","volume":"18","author":"Goetzl","year":"2004","journal-title":"FASEB J."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Bravo, G.\u00c1., Cede\u00f1o, R.R., Casadevall, M.P., and Rami\u00f3-Torrent\u00e0, L. (2022). Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway Modulators, from Current Insights to Future Perspectives. Cells, 11.","DOI":"10.3390\/cells11132058"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1080\/17425255.2022.2138330","article-title":"Current status and new developments in sphingosine-1-phosphate receptor antagonism: Fingolimod and more","volume":"18","author":"Constantinescu","year":"2022","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/14656566.2023.2178898","article-title":"An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis","volume":"24","author":"Dumitrescu","year":"2023","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1002\/jbmr.3844","article-title":"Cytokine-Induced and Stretch-Induced Sphingosine 1-Phosphate Production by Enthesis Cells Could Favor Abnormal Ossification in Spondyloarthritis","volume":"34","author":"Briolay","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1016\/j.cellsig.2010.05.022","article-title":"FTY720 and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1 and promote its proteasomal degradation in human pulmonary artery smooth muscle, breast cancer and androgen-independent prostate cancer cells","volume":"22","author":"Tonelli","year":"2010","journal-title":"Cell Signal."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Tachibana, K., Kusumoto, K., Ogawa, M., Ando, H., Shimizu, T., Ishima, Y., Ishida, T., and Okuhira, K. (2022). FTY720 Reduces Lipid Accumulation by Upregulating ABCA1 through Liver X Receptor and Sphingosine Kinase 2 Signaling in Macrophages. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314617"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1365-3083.2011.02528.x","article-title":"Sphingosine 1-phosphate receptor modulator FTY720 suppresses rat experimental autoimmune prostatitis","volume":"73","author":"Zhang","year":"2011","journal-title":"Scand. J. Immunol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1038\/s41598-017-06142-x","article-title":"Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Gonzalez, P., Debnath, S., Chen, Y.-A., Hernandez, E., Jha, P., Dakanali, M., Hsieh, J.-T., and Sun, X. (2023). A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020481"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ccr.2006.02.023","article-title":"Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages","volume":"9","author":"Visentin","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1158\/1078-0432.CCR-14-2031","article-title":"Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer","volume":"21","author":"Zhang","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"17717","DOI":"10.1073\/pnas.0906153106","article-title":"The crystal structure of sphingosine-1-phosphate in complex with a Fab fragment reveals metal bridging of an antibody and its antigen","volume":"106","author":"Wojciak","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1194\/jlr.M900048-JLR200","article-title":"Production and characterization of monoclonal anti-sphingosine-1-phosphate antibodies","volume":"50","author":"Jones","year":"2009","journal-title":"J. Lipid. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1002\/cncr.30393","article-title":"A phase 2 study of the sphingosine-1-phosphate antibody sonepcizumab in patients with metastatic renal cell carcinoma","volume":"123","author":"Pal","year":"2017","journal-title":"Cancer"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"115941","DOI":"10.1016\/j.bmc.2020.115941","article-title":"Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors","volume":"30","author":"Li","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/s41419-022-05049-4","article-title":"Targeting sphingosine kinase 1\/2 by a novel dual inhibitor SKI-349 suppresses non-small cell lung cancer cell growth","volume":"13","author":"Xue","year":"2022","journal-title":"Cell Death Dis."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2732\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:33:44Z","timestamp":1760124824000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,12]]},"references-count":163,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["cancers15102732"],"URL":"https:\/\/doi.org\/10.3390\/cancers15102732","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,12]]}}}