Skip to content
2000
Volume 18, Issue 1
  • ISSN: 2949-6810
  • E-ISSN: 2949-6829

Abstract

Sphingolipids are bioactive lipids that are essential for cellular functions like signaling, apoptosis, and proliferation. They are also important in the biology of cancer. The complex dynamics of sphingolipid metabolism and its consequences for the advancement of cancer are examined in this review. It highlights the regulatory functions of important enzymes such as ceramide kinase (CERK) and sphingosine kinases (SPHKs) in preserving the equilibrium between sphingosine-1-phosphate (S1P), a pro-survival chemical, and ceramides, which encourage cell death. Tumour growth, metastasis, and treatment resistance are all significantly affected by disturbances in this equilibrium. The review emphasizes the potential of sphingolipids as biomarkers for cancer prognosis and stratification, providing information on the course of the disease and the effectiveness of treatment. Their crucial functions in cellular signalling pathways that affect angiogenesis, immunological evasion, and drug resistance, all of which are linked to cancer, are also reviewed. Their role in the tumor microenvironment further highlights sphingolipids' significance as targets for novel therapeutic approaches. Improved clinical results and personalized cancer treatments are made possible by developments in sphingolipid biology and their potential as biomarkers. This thorough synthesis provides the groundwork for further studies that will use sphingolipid metabolism and signalling to create potent cancer treatments. In the fight against cancer, we can improve therapeutic efficacy and diagnostic accuracy by understanding these intricate relationships.

Loading

Article metrics loading...

/content/journals/dmbl/10.2174/0118723128377799250214075521
2025-02-26
2025-10-25
Loading full text...

Full text loading...

References

  1. RajpalS. KumarA. JoeW. Economic burden of cancer in India: Evidence from cross-sectional nationally representative household survey, 2014.PLoS One2018132e019332010.1371/journal.pone.0193320 29481563
    [Google Scholar]
  2. HassanpourS.H. DehghaniM. Review of cancer from perspective of molecular.J. Cancer Res. Pract.20174412712910.1016/j.jcrpr.2017.07.001
    [Google Scholar]
  3. FraumeniJ.F.Jr Epidemiologic approaches to cancer etiology.Annu. Rev. Public Health1982318510010.1146/annurev.pu.03.050182.000505 6293517
    [Google Scholar]
  4. YouldenD.R. CrambS.M. DunnN.A.M. MullerJ.M. PykeC.M. BaadeP.D. The descriptive epidemiology of female breast cancer: An international comparison of screening, incidence, survival and mortality.Cancer Epidemiol.201236323724810.1016/j.canep.2012.02.007. 22459198
    [Google Scholar]
  5. AugustineD. KhanW. RaoR. PatilS. AwanK. SowmyaS. HaragannavarV. PrasadK. Lipid metabolism in cancer: A systematic review.J. Carcinog.2021201410.4103/jcar.JCar_15_20 34321955
    [Google Scholar]
  6. TorreL.A. BrayF. SiegelR.L. FerlayJ. Lortet-TieulentJ. JemalA. Global cancer statistics, 2012.CA Cancer J. Clin.20156528710810.3322/caac.21262 25651787
    [Google Scholar]
  7. FeinbergA.P. FallinM.D. Epigenetics at the crossroads of genes and the environment.JAMA2015314111129113010.1001/jama.2015.10414 26372577
    [Google Scholar]
  8. ButlerL.M. PeroneY. DehairsJ. LupienL.E. de LaatV. TalebiA. LodaM. KinlawW.B. SwinnenJ.V. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention.Adv. Drug Deliv. Rev.202015924529310.1016/j.addr.2020.07.013 32711004
    [Google Scholar]
  9. SwinnenJ.V. BrusselmansK. VerhoevenG. Increased lipogenesis in cancer cells: New players, novel targets.Curr. Opin. Clin. Nutr. Metab. Care20069435836510.1097/01.mco.0000232894.28674.30 16778563
    [Google Scholar]
  10. WarburgO. WindF. NegeleinE. The metabolism of tumors in the body.J. Gen. Physiol.19278651953010.1085/jgp.8.6.519 19872213
    [Google Scholar]
  11. BaenkeF. PeckB. MiessH. SchulzeA. Hooked on fat: The role of lipid synthesis in cancer metabolism and tumour development.Dis. Model. Mech.2013661353136310.1242/dmm.011338 24203995
    [Google Scholar]
  12. HuangC. FreterC. Lipid metabolism, apoptosis and cancer therapy.Int. J. Mol. Sci.201516192494910.3390/ijms16010924 25561239
    [Google Scholar]
  13. LiL. HanJ. WangZ. LiuJ. WeiJ. XiongS. ZhaoZ. Mass spectrometry methodology in lipid analysis.Int. J. Mol. Sci.2014156104921050710.3390/ijms150610492 24921707
    [Google Scholar]
  14. LydicT.A. GooY.H. Lipidomics unveils the complexity of the lipidome in metabolic diseases.Clin. Transl. Med.201871e410.1186/s40169‑018‑0182‑9 29374337
    [Google Scholar]
  15. HanahanD. WeinbergR.A. Hallmarks of cancer: The next generation.Cell2011144564667410.1016/j.cell.2011.02.013 21376230
    [Google Scholar]
  16. LongJ. ZhangC.J. ZhuN. DuK. YinY.F. TanX. LiaoD.F. QinL. Lipid metabolism and carcinogenesis, cancer development.Am. J. Cancer Res.201885778791 29888102
    [Google Scholar]
  17. CorsettoP.A. ZavaS. RizzoA.M. ColomboI. The critical impact of sphingolipid metabolism in breast cancer progression and drug response.Int. J. Mol. Sci.2023243210710.3390/ijms24032107 36768427
    [Google Scholar]
  18. SaddoughiS.A. SongP. OgretmenB. Roles of bioactive sphingolipids in cancer biology and therapeutics.Subcell. Biochem.20084941344010.1007/978‑1‑4020‑8831‑5_16
    [Google Scholar]
  19. QuinvilleB.M. DeschenesN.M. RyckmanA.E. WaliaJ.S. A comprehensive review: Sphingolipid metabolism and implications of disruption in sphingolipid homeostasis.Int. J. Mol. Sci.20212211579310.3390/ijms22115793 34071409
    [Google Scholar]
  20. GaultC.R. ObeidL.M. HannunY.A. An overview of sphingolipid metabolism: From synthesis to breakdown.Adv. Exp. Med. Biol.201068812310.1007/978‑1‑4419‑6741‑1_1 20919643
    [Google Scholar]
  21. StorozhenkoG. KharchenkoV. KrasilnikovaO. TkachenkoO. Overview of concepts of the sphingolipid metabolism.Sci. Rise Biol. Sci.2021227232710.15587/2519‑8025.2021.234699
    [Google Scholar]
  22. LiR.Z. WangX.R. WangJ. XieC. WangX.X. PanH.D. MengW.Y. LiangT.L. LiJ.X. YanP.Y. WuQ.B. LiuL. YaoX.J. LeungE.L.H. The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance.Front. Oncol.20221294164310.3389/fonc.2022.941643 35965565
    [Google Scholar]
  23. SandhoffK. Neuronal sphingolipidoses: Membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism.Biochimie201613014615110.1016/j.biochi.2016.05.004 27157270
    [Google Scholar]
  24. GuptaP. TaiyabA. HussainA. AlajmiM.F. IslamA. HassanM.I. Targeting the sphingosine Kinase/Sphingosine-1-Phosphate signaling axis in drug discovery for cancer therapy.Cancers 2021138189810.3390/cancers13081898 33920887
    [Google Scholar]
  25. HannunY.A. ObeidL.M. Principles of bioactive lipid signalling: Lessons from sphingolipids.Nat. Rev. Mol. Cell Biol.20089213915010.1038/nrm2329 18216770
    [Google Scholar]
  26. AcharyaU. AcharyaJ.K. Enzymes of Sphingolipid metabolism in Drosophila melanogaster.Cell. Mol. Life Sci.200562212814210.1007/s00018‑004‑4254‑1 15666085
    [Google Scholar]
  27. HanadaK. Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism.Biochim. Biophys. Acta Mol. Cell Biol. Lipids200316321-3163010.1016/S1388‑1981(03)00059‑3 12782147
    [Google Scholar]
  28. HanadaK. KumagaiK. TomishigeN. YamajiT. CERT-mediated trafficking of ceramide.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20091791768469110.1016/j.bbalip.2009.01.006 19416656
    [Google Scholar]
  29. ZeidanY.H. HannunY.A. Translational aspects of sphingolipid metabolism.Trends Mol. Med.200713832733610.1016/j.molmed.2007.06.002 17588815
    [Google Scholar]
  30. Pralhada RaoR. VaidyanathanN. RengasamyM. Mammen OommenA. SomaiyaN. JagannathM.R. Sphingolipid metabolic pathway: An overview of major roles played in human diseases.J. Lipids2013201311210.1155/2013/178910 23984075
    [Google Scholar]
  31. KolterT. SandhoffK. Principles of lysosomal membrane digestion: Stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids.Annu. Rev. Cell Dev. Biol.20052118110310.1146/annurev.cellbio.21.122303.120013 16212488
    [Google Scholar]
  32. FunatoK. RiezmanH. Vesicular and nonvesicular transport of ceramide from ER to the Golgi apparatus in yeast.J. Cell Biol.2001155694996010.1083/jcb.200105033 11733544
    [Google Scholar]
  33. HanadaK. KumagaiK. YasudaS. MiuraY. KawanoM. FukasawaM. NishijimaM. Molecular machinery for non-vesicular trafficking of ceramide.Nature2003426696880380910.1038/nature02188 14685229
    [Google Scholar]
  34. MerrillA.H. SandhoffK. Sphingolipids: Metabolism and cell signaling. In: New Comprehensive Biochemistry; Elsevier:,20023637340710.1016/S0167‑7306(02)36016‑2
    [Google Scholar]
  35. KramerR. BielawskiJ. Kistner-GriffinE. OthmanA. AlecuI. ErnstD. Kornhauser; Hornemann, T.; Spassieva, S. Neurotoxic 1‐deoxysphingolipids and paclitaxel‐induced peripheral neuropathy.FASEB J.201529114461447210.1096/fj.15‑272567 26198449
    [Google Scholar]
  36. BeckerK.A. UerschelsA.K. GoinsL. DoolenS. McQuerryK.J. BielawskiJ. SureU. BieberichE. TaylorB.K. GulbinsE. SpassievaS.D. Role of 1‐Deoxysphingolipids in docetaxel neurotoxicity.J. Neurochem.2020154666267210.1111/jnc.14985 32058598
    [Google Scholar]
  37. BodeH. BourquinF. SuriyanarayananS. WeiY. AlecuI. OthmanA. Von EckardsteinA. HornemannT. HSAN1 mutations in serine palmitoyltransferase reveal a close structure–function–phenotype relationship.Hum. Mol. Genet.201625585386510.1093/hmg/ddv611 26681808
    [Google Scholar]
  38. HanG. Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities.Proc. Natl. Acad. Sci. USA2009106208186819110.1073/pnas.0905301106
    [Google Scholar]
  39. SiowD.L. WattenbergB.W. Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis.J. Biol. Chem.201228748401984020410.1074/jbc.C112.404012 23066021
    [Google Scholar]
  40. BreslowD.K. CollinsS.R. BodenmillerB. AebersoldR. SimonsK. ShevchenkoA. EjsingC.S. WeissmanJ.S. Orm family proteins mediate sphingolipid homeostasis.Nature201046372841048105310.1038/nature08787 20182505
    [Google Scholar]
  41. MuJ. LamS.M. ShuiG. Emerging roles and therapeutic potentials of sphingolipids in pathophysiology: Emphasis on fatty acyl heterogeneity.J. Genet. Genomics202351326827810.1016/j.jgg.2023.06.006 37364711
    [Google Scholar]
  42. MontavociL. RomanoD. ColomboL. ZuluetaA. CasM.D. ScavoneM. TosiD. BernardelliC. AutelitanoA. TrincheraM. RossettiL. CarettiA. Use of Myriocin as co-adjuvant in glaucoma surgery: An in vitro study.Int. J. Biochem. Cell Biol.202417710669910.1016/j.biocel.2024.106699 39571676
    [Google Scholar]
  43. JangH. OjhaU. JeongJ.H. ParkK.G. LeeS.Y. LeeY.M. Myriocin suppresses tumor growth by modulating macrophage polarization and function through the PI3K/Akt/mTOR pathway.Arch. Pharm. Res.202346762964510.1007/s12272‑023‑01454‑1 37468765
    [Google Scholar]
  44. ThomasR.J. OleinikN. Panneer SelvamS. VaenaS.G. DanyM. NgangaR.N. DepalmaR. BaronK.D. KimJ. SzulcZ.M. OgretmenB. HPV/E7 induces chemotherapy‐mediated tumor suppression by ceramide‐dependent mitophagy.EMBO Mol. Med.2017981030105110.15252/emmm.201607088 28606997
    [Google Scholar]
  45. Ghanbari MovahedZ. Rastegari-PouyaniM. MohammadiM. MansouriK. Cancer cells change their glucose metabolism to overcome increased ROS: One step from cancer cell to cancer stem cell?Biomed. Pharmacother.201911210869010.1016/j.biopha.2019.108690 30798124
    [Google Scholar]
  46. ParkW.J. BrennerO. Kogot-LevinA. SaadaA. MerrillA.H.Jr Pewzner-JungY. FutermanA.H. Development of pheochromocytoma in ceramide synthase 2 null mice.Endocr. Relat. Cancer201522462363210.1530/ERC‑15‑0058 26113602
    [Google Scholar]
  47. FekryB. JeffriesK.A. EsmaeilniakooshkghaziA. OgretmenB. KrupenkoS.A. KrupenkoN.I. CerS6 is a novel transcriptional target of p53 protein activated by non-genotoxic stress.J. Biol. Chem.201629132165861659610.1074/jbc.M116.716902 27302066
    [Google Scholar]
  48. White-GilbertsonS. MullenT. SenkalC. LuP. OgretmenB. ObeidL. Voelkel-JohnsonC. Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells.Oncogene20092881132114110.1038/onc.2008.468 19137010
    [Google Scholar]
  49. Meyers-NeedhamM. PonnusamyS. GencerS. JiangW. ThomasR.J. SenkalC.E. OgretmenB. Concerted functions of HDAC1 and microRNA‐574‐5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells.EMBO Mol. Med.201242789210.1002/emmm.201100189 22180294
    [Google Scholar]
  50. LoiseauN. PolizziA. DupuyA. ThervilleN. RakotonirainyM. LoyJ. ViadereJ.L. CossalterA.M. BaillyJ.D. PuelO. Kolf-ClauwM. Bertrand-MichelJ. LevadeT. GuillouH. OswaldI.P. New insights into the organ-specific adverse effects of fumonisin B1: Comparison between lung and liver.Arch. Toxicol.20158991619162910.1007/s00204‑014‑1323‑6 25155190
    [Google Scholar]
  51. RahmaniyanM. CurleyR.W.Jr ObeidL.M. HannunY.A. KravekaJ.M. Identification of dihydroceramide desaturase as a direct in vitro target for fenretinide.J. Biol. Chem.201128628247542476410.1074/jbc.M111.250779 21543327
    [Google Scholar]
  52. OrientiI. FrancescangeliF. De AngelisM.L. FecchiK. Bongiorno-BorboneL. SignoreM. PeschiaroliA. BoeA. BrusellesA. CostantinoA. EramoA. SalvatiV. SetteG. ContavalliP. ZollaL. OkiT. KitamuraT. SpadaM. GiulianiA. BaiocchiM. La TorreF. MelinoG. TartagliaM. De MariaR. ZeunerA. A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors.Cell Death Dis.201910752910.1038/s41419‑019‑1775‑y 31332161
    [Google Scholar]
  53. AirolaM.V. ShanbhogueP. ShamseddineA.A. GujaK.E. SenkalC.E. MainiR. BartkeN. WuB.X. ObeidL.M. Garcia-DiazM. HannunY.A. Structure of human nSMase2 reveals an interdomain allosteric activation mechanism for ceramide generation.Proc. Natl. Acad. Sci. USA201711428E5549E555810.1073/pnas.1705134114 28652336
    [Google Scholar]
  54. GorelikA. IllesK. HeinzL.X. Superti-FurgaG. NagarB. Crystal structure of mammalian acid sphingomyelinase.Nat. Commun.2016711219610.1038/ncomms12196 27435900
    [Google Scholar]
  55. SantanaP. PeñaL.A. Haimovitz-FriedmanA. MartinS. GreenD. McLoughlinM. Cordon-CardoC. SchuchmanE.H. FuksZ. KolesnickR. Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis.Cell199686218919910.1016/S0092‑8674(00)80091‑4 8706124
    [Google Scholar]
  56. LadduA.R. SomaniP. Desipramine toxicity and its treatment.Toxicol. Appl. Pharmacol.196915228729410.1016/0041‑008X(69)90029‑5 5804746
    [Google Scholar]
  57. DegagnéE. PanduranganA. BandhuvulaP. KumarA. EltanawyA. ZhangM. YoshinagaY. NefedovM. de JongP.J. FongL.G. YoungS.G. BittmanR. AhmediY. SabaJ.D. Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs.J. Clin. Invest.2014124125368538410.1172/JCI74188 25347472
    [Google Scholar]
  58. OgretmenB. Sphingolipid metabolism in cancer signalling and therapy.Nat. Rev. Cancer2018181335010.1038/nrc.2017.96 29147025
    [Google Scholar]
  59. FuruyaH. ShimizuY. KawamoriT. Sphingolipids in cancer.Cancer Metastasis Rev.2011303-456757610.1007/s10555‑011‑9304‑1 22005951
    [Google Scholar]
  60. FuY. ZouT. ShenX. NelsonP.J. LiJ. WuC. YangJ. ZhengY. BrunsC. ZhaoY. QinL. DongQ. Lipid metabolism in cancer progression and therapeutic strategies.MedComm202121275910.1002/mco2.27 34766135
    [Google Scholar]
  61. MorignyP. ZuberJ. HaidM. KalteneckerD. RiolsF. LimaJ.D.C. SimoesE. OtochJ.P. SchmidtS.F. HerzigS. AdamskiJ. SeelaenderM. Berriel DiazM. RohmM. High levels of modified ceramides are a defining feature of murine and human cancer cachexia.J. Cachexia Sarcopenia Muscle20201161459147510.1002/jcsm.12626 33090732
    [Google Scholar]
  62. WangS. LiangY. ChangW. HuB. ZhangY. Triple negative breast cancer depends on sphingosine kinase 1 (Sphk1)/sphingos ine-1-phosphate (s1p)/sphingosine1-phosphate receptor 3 (s1pr3)/notch signaling for metastasis.Med. Sci. Monit.2018241912192310.12659/MSM.905833 29605826
    [Google Scholar]
  63. HaitN.C. MaitiA. The role of sphingosine-1-phosphate and ceramide-1-phosphate in inflammation and cancer.Mediators Inflamm.2017201711710.1155/2017/4806541 29269995
    [Google Scholar]
  64. AlshakerH. ThrowerH. PchejetskiD. Sphingosine kinase 1 in breast cancer-A new molecular marker and a therapy target.Front. Oncol.20201028910.3389/fonc.2020.00289
    [Google Scholar]
  65. ZhangL. WangX. BullockA.J. CalleaM. ShahH. SongJ. MorenoK. VisentinB. DeutschmanD. AlsopD.C. AtkinsM.B. MierJ.W. SignorettiS. BhasinM. SabbadiniR.A. BhattR.S. Anti-S1P antibody as a novel therapeutic strategy for VEGFR TKI-resistant renal cancer.Clin. Cancer Res.20152181925193410.1158/1078‑0432.CCR‑14‑2031 25589614
    [Google Scholar]
  66. TerzićJ. GrivennikovS. KarinE. KarinM. Inflammation and colon cancer.Gastroenterology2010138621012114.e510.1053/j.gastro.2010.01.058 20420949
    [Google Scholar]
  67. NagahashiM. TakabeK. TerracinaK.P. SomaD. HiroseY. KobayashiT. MatsudaY. WakaiT. Sphingosine-1-phosphate transporters as targets for cancer therapy.BioMed Res. Int.201420141710.1155/2014/651727 25133174
    [Google Scholar]
  68. TakabeK. PaughS.W. MilstienS. SpiegelS. “Inside-out” signaling of sphingosine-1-phosphate: therapeutic targets.Pharmacol. Rev.200860218119510.1124/pr.107.07113 18552276
    [Google Scholar]
  69. WangP. YuanY. LinW. ZhongH. XuK. QiX. Roles of sphingosine-1-phosphate signaling in cancer.Cancer Cell Int.201919129510.1186/s12935‑019‑1014‑8 31807117
    [Google Scholar]
  70. StrubG.M. MaceykaM. HaitN.C. MilstienS. SpiegelS. Extracellular and intracellular actions of sphingosine-1-phosphate.Adv. Exp. Med. Biol.201068814115510.1007/978‑1‑4419‑6741‑1_10 20919652
    [Google Scholar]
  71. MaceykaM. SankalaH. HaitN.C. Le StunffH. LiuH. TomanR. CollierC. ZhangM. SatinL.S. MerrillA.H.Jr MilstienS. SpiegelS. SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism.J. Biol. Chem.200528044371183712910.1074/jbc.M502207200 16118219
    [Google Scholar]
  72. TakabeK. KimR.H. AllegoodJ.C. MitraP. RamachandranS. NagahashiM. HarikumarK.B. HaitN.C. MilstienS. SpiegelS. Estradiol induces export of sphingosine 1-phosphate from breast cancer cells via ABCC1 and ABCG2.J. Biol. Chem.201028514104771048610.1074/jbc.M109.064162 20110355
    [Google Scholar]
  73. TakabeK. SpiegelS. Export of sphingosine-1-phosphate and cancer progression.J. Lipid Res.20145591839184610.1194/jlr.R046656 24474820
    [Google Scholar]
  74. SurhY-J. Abstract ED01-01: Targeting inflammatory microenvironment for cancer chemoprevention and therapy.Cancer Prev. Res. 20136Suppl. 11ED010110.1158/1940‑6215.PREV‑13‑ED01‑01
    [Google Scholar]
  75. HanyuT. NagahashiM. IchikawaH. IshikawaT. KobayashiT. WakaiT. Expression of phosphorylated sphingosine kinase 1 is associated with diffuse type and lymphatic invasion in human gastric cancer.Surgery201816361301130610.1016/j.surg.2017.11.024 29370930
    [Google Scholar]
  76. NagahashiM. YamadaA. KatsutaE. AoyagiT. HuangW.C. TerracinaK.P. HaitN.C. AllegoodJ.C. TsuchidaJ. YuzaK. NakajimaM. AbeM. SakimuraK. MilstienS. WakaiT. SpiegelS. TakabeK. Targeting the SphK1/S1P/S1PR1 axis that links obesity, chronic inflammation, and breast cancer metastasis.Cancer Res.20187871713172510.1158/0008‑5472.CAN‑17‑1423 29351902
    [Google Scholar]
  77. HaitN.C. AllegoodJ. MaceykaM. StrubG.M. HarikumarK.B. SinghS.K. LuoC. MarmorsteinR. KordulaT. MilstienS. SpiegelS. Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate.Science200932559451254125710.1126/science.1176709 19729656
    [Google Scholar]
  78. AlvarezS.E. HarikumarK.B. HaitN.C. AllegoodJ. StrubG.M. KimE.Y. MaceykaM. JiangH. LuoC. KordulaT. MilstienS. SpiegelS. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2.Nature201046573011084108810.1038/nature09128 20577214
    [Google Scholar]
  79. NagahashiM. TakabeK. LiuR. PengK. WangX. WangY. HaitN.C. WangX. AllegoodJ.C. YamadaA. AoyagiT. LiangJ. PandakW.M. SpiegelS. HylemonP.B. ZhouH. Conjugated bile acid–activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression.Hepatology20156141216122610.1002/hep.27592 25363242
    [Google Scholar]
  80. HaitN.C. WiseL.E. AllegoodJ.C. O’BrienM. AvniD. ReevesT.M. KnappP.E. LuJ. LuoC. MilesM.F. MilstienS. LichtmanA.H. SpiegelS. Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory.Nat. Neurosci.201417797198010.1038/nn.3728 24859201
    [Google Scholar]
  81. JinL. LiuW.R. TianM.X. FanJ. ShiY.H. The SphKs/S1P/S1PR1 axis in immunity and cancer: More ore to be mined.World J. Surg. Oncol.201614113110.1186/s12957‑016‑0884‑7 27129720
    [Google Scholar]
  82. OliveraA. MizugishiK. TikhonovaA. CiacciaL. OdomS. ProiaR.L. RiveraJ. The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis.Immunity200726328729710.1016/j.immuni.2007.02.008 17346996
    [Google Scholar]
  83. MendelsonK. ZygmuntT. Torres-VázquezJ. EvansT. HlaT. Sphingosine1-phosphate receptor signaling regulates proper embryonic vascular patterning.J. Biol. Chem.201328842143215610.1074/jbc.M112.427344 23229546
    [Google Scholar]
  84. KawaharaA. NishiT. HisanoY. FukuiH. YamaguchiA. MochizukiN. The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors.Science2009323591352452710.1126/science.1167449 19074308
    [Google Scholar]
  85. OsborneN. Brand-ArzamendiK. OberE.A. JinS.W. VerkadeH. HoltzmanN.G. YelonD. StainierD.Y.R. The spinster homolog, two of hearts, is required for sphingosine 1-phosphate signaling in zebrafish.Curr. Biol.200818231882188810.1016/j.cub.2008.10.061 19062281
    [Google Scholar]
  86. MoroK. KawaguchiT. TsuchidaJ. GabrielE. QiQ. YanL. WakaiT. TakabeK. NagahashiM. Ceramide species are elevated in human breast cancer and are associated with less aggressiveness.Oncotarget2018928198741989010.18632/oncotarget.24903 29731990
    [Google Scholar]
  87. NeubauerH.A. PitsonS.M. Roles, regulation and inhibitors of sphingosine kinase 2.FEBS J.2013280215317533610.1111/febs.12314
    [Google Scholar]
  88. SobueS. IwasakiT. SugisakiC. NagataK. KikuchiR. MurakamiM. TakagiA. KojimaT. BannoY. AkaoY. NozawaY. KannagiR. SuzukiM. AbeA. NaoeT. MurateT. Quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia and myelodysplastic syndromes.Leukemia200620112042204610.1038/sj.leu.2404386 16990773
    [Google Scholar]
  89. RuckhäberleE. RodyA. EngelsK. GaetjeR. von MinckwitzG. SchiffmannS. GröschS. GeisslingerG. HoltrichU. KarnT. KaufmannM. Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer.Breast Cancer Res. Treat.20081121415210.1007/s10549‑007‑9836‑9 18058224
    [Google Scholar]
  90. SutphenR. XuY. WilbanksG.D. FioricaJ. GrendysE.C.Jr LaPollaJ.P. ArangoH. HoffmanM.S. MartinoM. WakeleyK. GriffinD. BlancoR.W. CantorA.B. XiaoY. KrischerJ.P. Lysophospholipids are potential biomarkers of ovarian cancer.Cancer Epidemiol. Biomarkers Prev.20041371185119110.1158/1055‑9965.1185.13.7 15247129
    [Google Scholar]
  91. HongG. BaudhuinL.M. XuY. Sphingosine‐1‐phosphate modulates growth and adhesion of ovarian cancer cells.FEBS Lett.1999460351351810.1016/S0014‑5793(99)01400‑3 10556527
    [Google Scholar]
  92. AlvarezS.E. MilstienS. SpiegelS. Autocrine and paracrine roles of sphingosine-1-phosphate.Trends Endocrinol. Metab.200718830030710.1016/j.tem.2007.07.005 17904858
    [Google Scholar]
  93. PitsonS.M. MorettiP.A. ZebolJ.R. LynnH.E. XiaP. VadasM.A. WattenbergB.W. Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation.EMBO J.200322205491550010.1093/emboj/cdg540 14532121
    [Google Scholar]
  94. HobsonJ.P. RosenfeldtH.M. BarakL.S. OliveraA. PoultonS. CaronM.G. MilstienS. SpiegelS. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility.Science200129155091800180310.1126/science.1057559 11230698
    [Google Scholar]
  95. StahelinR.V. HwangJ.H. KimJ.H. ParkZ.Y. JohnsonK.R. ObeidL.M. ChoW. The mechanism of membrane targeting of human sphingosine kinase 1.J. Biol. Chem.200528052430304303810.1074/jbc.M507574200 16243846
    [Google Scholar]
  96. PitsonS.M. XiaP. LeclercqT.M. MorettiP.A.B. ZebolJ.R. LynnH.E. WattenbergB.W. VadasM.A. Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling.J. Exp. Med.20052011495410.1084/jem.20040559 15623571
    [Google Scholar]
  97. DöllF. PfeilschifterJ. HuwilerA. The epidermal growth factor stimulates sphingosine kinase-1 expression and activity in the human mammary carcinoma cell line MCF7.Biochim. Biophys. Acta Mol. Cell Biol. Lipids200517381-3728110.1016/j.bbalip.2005.12.001 16414307
    [Google Scholar]
  98. ShidaD. TakabeK. KapitonovD. MilstienS. SpiegelS. Targeting SphK1 as a new strategy against cancer.Curr. Drug Targets20089866267310.2174/138945008785132402 18691013
    [Google Scholar]
  99. Pulkoski-GrossM.J. ObeidL.M. Molecular mechanisms of regulation of sphingosine kinase 1.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20181863111413142210.1016/j.bbalip.2018.08.015 30591148
    [Google Scholar]
  100. NicholasS.E. RowseyT.G. PriyadarsiniS. MandalN.A. KaramichosD. Unravelling the interplay of sphingolipids and TGF-β signaling in the human corneal stroma.PLoS One2017128e018239010.1371/journal.pone.0182390 28806736
    [Google Scholar]
  101. HatoumD. HaddadiN. LinY. NassifN.T. McGowanE.M. Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: Challenges for SphK as an oncotarget.Oncotarget2017822368983692910.18632/oncotarget.16370 28415564
    [Google Scholar]
  102. PaulB. LewinskaM. AndersenJ.B. Lipid alterations in chronic liver disease and liver cancer.JHEP Reports20224610047910.1016/j.jhepr.2022.100479 35469167
    [Google Scholar]
  103. HartP.C. ChiyodaT. LiuX. WeigertM. CurtisM. ChiangC.Y. LothR. LastraR. McGregorS.M. LocasaleJ.W. LengyelE. RomeroI.L. SPHK1 is a novel target of metformin in ovarian cancer.Mol. Cancer Res.201917487088110.1158/1541‑7786.MCR‑18‑0409 30655321
    [Google Scholar]
  104. DingX. ZhangY. HuangT. XuG. PengC. ChenG. KongB. FriessH. ShenS. LvY. RobertsL.R. WangL. ZouX. Targeting sphingosine kinase 2 suppresses cell growth and synergizes with BCL2/BCL-XL inhibitors through NOXA-mediated MCL1 degradation in cholangiocarcinoma.Am. J. Cancer Res.201993546561 30949409
    [Google Scholar]
  105. CannavoA. LiccardoD. KomiciK. CorbiG. de LuciaC. FemminellaG.D. EliaA. BencivengaL. FerraraN. KochW.J. PaolocciN. RengoG. Sphingosine kinases and sphingosine 1-phosphate receptors: Signaling and actions in the cardiovascular system.Front. Pharmacol.20178AUG55610.3389/fphar.2017.00556 28878674
    [Google Scholar]
  106. HasanifardL. SheervalilouR. MajidiniaM. YousefiB. New insights into the roles and regulation of SphK2 as a therapeutic target in cancer chemoresistance.J. Cell. Physiol.201923468162818110.1002/jcp.27612 30456838
    [Google Scholar]
  107. XuD. ZhuH. WangC. ZhaoW. LiuG. BaoG. CuiD. FanJ. WangF. JinH. CuiZ. SphK2 over-expression promotes osteosarcoma cell growth.Oncotarget201786210552510553510.18632/oncotarget.22314 29285269
    [Google Scholar]
  108. Panneer SelvamS. De PalmaR.M. OaksJ.J. OleinikN. PetersonY.K. StahelinR.V. SkordalakesE. PonnusamyS. Garrett-MayerE. SmithC.D. OgretmenB. Binding of the sphingolipid S1P to hTERT stabilizes telomerase at the nuclear periphery by allosterically mimicking protein phosphorylation.Sci. Signal.20158381ra5810.1126/scisignal.aaa4998 26082434
    [Google Scholar]
  109. StrubG.M. PaillardM. LiangJ. GomezL. AllegoodJ.C. HaitN.C. MaceykaM. PriceM.M. ChenQ. SimpsonD.C. KordulaT. MilstienS. LesnefskyE.J. SpiegelS. Sphingosine‐1‐phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration.FASEB J.201125260061210.1096/fj.10‑167502 20959514
    [Google Scholar]
  110. NewtonJ. LimaS. MaceykaM. SpiegelS. Revisiting the sphingolipid rheostat: Evolving concepts in cancer therapy.Exp. Cell Res.2015333219520010.1016/j.yexcr.2015.02.025 25770011
    [Google Scholar]
  111. GaladariS. RahmanA. PallichankandyS. ThayyullathilF. Tumor suppressive functions of ceramide: Evidence and mechanisms.Apoptosis201520568971110.1007/s10495‑015‑1109‑1 25702155
    [Google Scholar]
  112. YoungM.M. KesterM. WangH.G. Sphingolipids: Regulators of crosstalk between apoptosis and autophagy.J. Lipid Res.201354151910.1194/jlr.R031278 23152582
    [Google Scholar]
  113. RamanathanR. OlexA.L. DozmorovM. BearH.D. FernandezL.J. TakabeK. Angiopoietin pathway gene expression associated with poor breast cancer survival.Breast Cancer Res. Treat.2017162119119810.1007/s10549‑017‑4102‑2 28062977
    [Google Scholar]
  114. Al-RashedF. AhmadZ. SniderA.J. ThomasR. KochumonS. MelhemM. SindhuS. ObeidL.M. Al-MullaF. HannunY.A. AhmadR. Ceramide kinase regulates TNF-α-induced immune responses in human monocytic cells.Sci. Rep.2021111825910.1038/s41598‑021‑87795‑7 33859296
    [Google Scholar]
  115. MitsutakeS. KimT.J. InagakiY. KatoM. YamashitaT. IgarashiY. Ceramide kinase is a mediator of calcium-dependent degranulation in mast cells.J. Biol. Chem.200427917175701757710.1074/jbc.M312885200 14769792
    [Google Scholar]
  116. ZhuS. XuY. WangL. LiaoS. WangY. ShiM. TuY. ZhouY. WeiW. Ceramide kinase mediates intrinsic resistance and inferior response to chemotherapy in triple‐negative breast cancer by upregulating Ras/ERK and PI3K/Akt pathways.Cancer Cell Int.20212114210.1186/s12935‑020‑01735‑5 33430896
    [Google Scholar]
  117. SchwalmS. ErhardtM. RömerI. PfeilschifterJ. Zangemeister-WittkeU. HuwilerA. Ceramide kinase is upregulated in metastatic breast cancer cells and contributes to migration and invasion by activation of PI 3-kinase and Akt.Int. J. Mol. Sci.2020214139610.3390/ijms21041396 32092937
    [Google Scholar]
  118. Gomez-LarrauriA. Das AdhikariU. Aramburu-NuñezM. CustodiaA. OuroA. Ceramide metabolism enzymes-therapeutic targets against cancer.Medicina 202157772910.3390/medicina57070729
    [Google Scholar]
  119. PayneA.W. PantD.K. PanT.C. ChodoshL.A. Ceramide kinase promotes tumor cell survival and mammary tumor recurrence.Cancer Res.201474216352636310.1158/0008‑5472.CAN‑14‑1292 25164007
    [Google Scholar]
  120. CamachoL. OuroA. Gomez-LarrauriA. CarracedoA. Gomez-MuñozA. Implication of ceramide kinase/C1P in cancer development and progression.Cancers 202214122710.3390/cancers14010227 35008391
    [Google Scholar]
  121. PierucciF. FratiA. BattistiniC. PennaF. CostelliP. MeacciE. Control of skeletal muscle atrophy associated to cancer or corticosteroids by ceramide kinase.Cancers 20211313328510.3390/cancers13133285 34209043
    [Google Scholar]
  122. Gómez-MuñozA. KongJ.Y. SalhB. SteinbrecherU.P. Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase in macrophages.J. Lipid Res.20044519910510.1194/jlr.M300158‑JLR200 14523050
    [Google Scholar]
  123. Gomez-LarrauriA. OuroA. TruebaM. Gomez-MuñozA. Regulation of cell growth, survival and migration by ceramide 1-phosphate - Implications in lung cancer progression and inflammation.Cell. Signal.20218310998010.1016/j.cellsig.2021.109980 33727076
    [Google Scholar]
  124. VincentA. HermanJ. SchulickR. HrubanR.H. GogginsM. Pancreatic cancer.Lancet2011378979160762010.1016/S0140‑6736(10)62307‑0 21620466
    [Google Scholar]
  125. RiveraI.G. OrdoñezM. PresaN. GangoitiP. Gomez-LarrauriA. TruebaM. FoxT. KesterM. Gomez-MuñozA. Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells.Biochem. Pharmacol.201610210711910.1016/j.bcp.2015.12.009 26707801
    [Google Scholar]
  126. CamachoL. Zabala-LetonaA. CortazarA.R. AstobizaI. Dominguez-HerreraA. ErcillaA. CrespoJ. VieraC. Fernández-RuizS. Martinez-GonzalezA. TorranoV. Martín-MartínN. Gomez-MuñozA. CarracedoA. Identification of androgen receptor metabolic correlome reveals the repression of ceramide kinase by androgens.Cancers 20211317430710.3390/cancers13174307 34503116
    [Google Scholar]
  127. WuL. RunkleC. JinH-J. YuJ. LiJ. YangX. KuzelT. LeeC. YuJ. CCN3/NOV gene expression in human prostate cancer is directly suppressed by the androgen receptor.Oncogene201433450451310.1038/onc.2012.602 23318417
    [Google Scholar]
  128. BhadwalP. DahiyaD. ShindeD. VaipheiK. MathR.G.H. RandhawaV. AgnihotriN. LC-HRMS based approach to identify novel sphingolipid biomarkers in breast cancer patients.Sci. Rep.2020101466810.1038/s41598‑020‑61283‑w 32170160
    [Google Scholar]
  129. RajputK. AnsariM.N. JhaS.K. PaniT. MedatwalN. ChattopadhyayS. BajajA. DasguptaU. Ceramide kinase (CERK) emerges as a common therapeutic target for triple positive and triple negative breast cancer cells.Cancers 20221418449610.3390/cancers14184496 36139656
    [Google Scholar]
  130. MitraP. MaceykaM. PayneS.G. LamourN. MilstienS. ChalfantC.E. SpiegelS. Ceramide kinase regulates growth and survival of A549 human lung adenocarcinoma cells.FEBS Lett.2007581473574010.1016/j.febslet.2007.01.041 17274985
    [Google Scholar]
  131. NunesJ. NaymarkM. SauerL. MuhammadA. KeunH. SturgeJ. StebbingJ. WaxmanJ. PchejetskiD. Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection.Br. J. Cancer2012106590991510.1038/bjc.2012.14 22315056
    [Google Scholar]
  132. SedićM. GrbčićP. PavelićS.K. Bioactive sphingolipids as biomarkers predictive of disease severity and treatment response in cancer: Current status and translational challenges.Anticancer Res.2019391415610.21873/anticanres.13078 30591439
    [Google Scholar]
  133. MalavaudB. PchejetskiD. MazerollesC. de PaivaG.R. CalvetC. DoumercN. PitsonS. RischmannP. CuvillierO. Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens.Eur. J. Cancer201046183417342410.1016/j.ejca.2010.07.053 20970322
    [Google Scholar]
  134. WallerL.P. DeshpandeV. PyrsopoulosN. Hepatocellular carcinoma: A comprehensive review.World J. Hepatol.20157262648266310.4254/wjh.v7.i26.2648 26609342
    [Google Scholar]
  135. UranbilegB. IkedaH. KuranoM. EnookuK. SatoM. SaigusaD. AokiJ. IshizawaT. HasegawaK. KokudoN. YatomiY. Increased mRNA levels of sphingosine kinases and S1P lyase and reduced levels of S1P were observed in hepatocellular carcinoma in association with poorer differentiation and earlier recurrence.PLoS One2016112e014946210.1371/journal.pone.0149462 26886371
    [Google Scholar]
  136. CaiH. XieX. JiL. RuanX. ZhengZ. Sphingosine kinase 1: A novel independent prognosis biomarker in hepatocellular carcinoma.Oncol. Lett.20171342316232210.3892/ol.2017.5732 28454397
    [Google Scholar]
  137. FitianA.I. NelsonD.R. LiuC. XuY. AraratM. CabreraR. Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS ‐ MS.Liver Int.20143491428144410.1111/liv.12541 24661807
    [Google Scholar]
  138. GrammatikosG. SchoellN. FerreirósN. BonD. HerrmannE. FarnikH. KöberleV. PiiperA. ZeuzemS. KronenbergerB. WaidmannO. PfeilschifterJ. Serum sphingolipidomic analyses reveal an upregulation of C16- ceramide and sphingosine-1-phosphate in hepatocellular carcinoma.Oncotarget2016714180951810510.18632/oncotarget.7741 26933996
    [Google Scholar]
  139. KrautbauerS. MeierE.M. Rein-FischboeckL. PohlR. WeissT.S. SigruenerA. AslanidisC. LiebischG. BuechlerC. Ceramide and polyunsaturated phospholipids are strongly reduced in human hepatocellular carcinoma.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20161861111767177410.1016/j.bbalip.2016.08.014 27570113
    [Google Scholar]
  140. KrautbauerS. WeissT.S. WiestR. SchachererD. LiebischG. BuechlerC. Diagnostic value of systemic cholesteryl ester/free cholesterol ratio in hepatocellular carcinoma.Anticancer Res.20173773527353510.21873/anticanres.11721 28668842
    [Google Scholar]
  141. TholeyR. SawickiJ.A. BrodyJ.R. Molecular-based and alternative therapies for pancreatic cancer: Looking “out of the box”.Cancer J.201218666567310.1097/PPO.0b013e3182793ff6 23187855
    [Google Scholar]
  142. JiangY. DiVittoreN. YoungM. JiaZ. XieK. RittyT. KesterM. FoxT. Altered sphingolipid metabolism in patients with metastatic pancreatic cancer.Biomolecules20133343544810.3390/biom3030435 24970174
    [Google Scholar]
  143. Di GangiI.M. MazzaT. FontanaA. CopettiM. FusilliC. IppolitoA. MattiviF. LatianoA. AndriulliA. VrhovsekU. PazienzaV. Metabolomic profile in pancreatic cancer patients: A consensus-based approach to identify highly discriminating metabolites.Oncotarget2016755815582910.18632/oncotarget.6808 26735340
    [Google Scholar]
  144. ArnoldM. SierraM.S. LaversanneM. SoerjomataramI. JemalA. BrayF. Global patterns and trends in colorectal cancer incidence and mortality.Gut201766468369110.1136/gutjnl‑2015‑310912 26818619
    [Google Scholar]
  145. FungK.Y.C. TaborB. BuckleyM.J. PriebeI.K. PurinsL. PompeiaC. BrierleyG.V. LockettT. GibbsP. TieJ. McMurrickP. MooreJ. RuszkiewiczA. NiceE. AdamsT.E. BurgessA. CosgroveL.J. Blood-based protein biomarker panel for the detection of colorectal cancer.PLoS One2015103e012042510.1371/journal.pone.0120425 25793510
    [Google Scholar]
  146. JunjunY. YaoH. YuanyuanZ. XiaoningZ. XiqiaoZ. Expression of sphingosine-1-phosphate receptor 2 in human colon cancer and its correlation with cancer migration and invasion.Gastroenterology20171525S102410.1016/S0016‑5085(17)33467‑4
    [Google Scholar]
  147. KawamoriT. KaneshiroT. OkumuraM. MaaloufS. UflackerA. BielawskiJ. HannunY.A. ObeidL.M. Role for sphingosine kinase 1 in colon carcinogenesis.FASEB J.200923240541410.1096/fj.08‑117572 18824518
    [Google Scholar]
  148. SamuhasaneetoS. PromagsornS. PunsawadC. Sphingosine 1-phosphate receptor 4 expression in colorectal cancer patients.Walailak J. Sci. Technol.2017148663669
    [Google Scholar]
  149. LongJ. XieY. YinJ. LuW. FangS. SphK1 promotes tumor cell migration and invasion in colorectal cancer.Tumour Biol.20163756831683610.1007/s13277‑015‑4542‑4 26662312
    [Google Scholar]
  150. TanS.S.L. KhinL.W. WongL. YanB. OngC.W. DattaA. Salto-TellezM. LamY. YapC.T. Sphingosine kinase 1 promotes malignant progression in colon cancer and independently predicts survival of patients with colon cancer by competing risk approach in South asian population.Clin. Transl. Gastroenterol.201452e5110.1038/ctg.2013.21 24572701
    [Google Scholar]
  151. RosaR. MarcianoR. MalapelleU. FormisanoL. NappiL. D’AmatoC. D’AmatoV. DamianoV. MarfèG. Del VecchioS. ZannettiA. GrecoA. De StefanoA. CarlomagnoC. VenezianiB.M. TronconeG. De PlacidoS. BiancoR. Sphingosine kinase 1 overexpression contributes to cetuximab resistance in human colorectal cancer models.Clin. Cancer Res.201319113814710.1158/1078‑0432.CCR‑12‑1050 23166225
    [Google Scholar]
  152. DaiX. LiT. BaiZ. YangY. LiuX. ZhanJ. ShiB. Breast cancer intrinsic subtype classification, clinical use and future trends.Am. J. Cancer Res.201551029292943 26693050
    [Google Scholar]
  153. NagahashiM. TsuchidaJ. MoroK. HasegawaM. TatsudaK. WoelfelI.A. TakabeK. WakaiT. High levels of sphingolipids in human breast cancer.J. Surg. Res.2016204243544410.1016/j.jss.2016.05.022 27565080
    [Google Scholar]
  154. NagahashiM. YamadaA. MiyazakiH. AllegoodJ.C. TsuchidaJ. AoyagiT. HuangW.C. TerracinaK.P. AdamsB.J. RashidO.M. MilstienS. WakaiT. SpiegelS. TakabeK. Interstitial fluid sphingosine-1-phosphate in murine mammary gland and cancer and human breast tissue and cancer determined by novel methods.J. Mammary Gland Biol. Neoplasia2016211-291710.1007/s10911‑016‑9354‑7 27194029
    [Google Scholar]
  155. DesaiS.A. PatelV.P. BhosleK.P. NagareS.D. ThombareK.C. The tumor microenvironment: Shaping cancer progression and treatment response.J. Chemother.2025371154410.1080/1120009X.2023.2300224 38179655
    [Google Scholar]
  156. TsuchidaJ. NagahashiM. NakajimaM. MoroK. TatsudaK. RamanathanR. TakabeK. WakaiT. Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis.J. Surg. Res.20162051859410.1016/j.jss.2016.06.022 27621003
    [Google Scholar]
  157. NagahashiM. RamachandranS. KimE.Y. AllegoodJ.C. RashidO.M. YamadaA. ZhaoR. MilstienS. ZhouH. SpiegelS. TakabeK. Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis.Cancer Res.201272372673510.1158/0008‑5472.CAN‑11‑216722298596
    [Google Scholar]
/content/journals/dmbl/10.2174/0118723128377799250214075521
Loading
/content/journals/dmbl/10.2174/0118723128377799250214075521
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keyword(s): biomarker; Cancer; lipid; melanoma cells; novel treatment; signaling pathway; sphingolipid
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test