Skip to content
2000
image of Sphingolipids in Cancer: Metabolism, Signaling, and Clinical Implications

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
2025-05-28
Loading full text...

Full text loading...

References

  1. Rajpal S. Kumar A. Joe W. Economic burden of cancer in India: Evidence from cross-sectional nationally representative household survey, 2014. PLoS One 2018 13 2 e0193320 10.1371/journal.pone.0193320 29481563
    [Google Scholar]
  2. Hassanpour S.H. Dehghani M. Review of cancer from perspective of molecular. J. Cancer Res. Pract. 2017 4 4 127 129 10.1016/j.jcrpr.2017.07.001
    [Google Scholar]
  3. Fraumeni J.F. Jr Epidemiologic approaches to cancer etiology. Annu. Rev. Public Health 1982 3 1 85 100 10.1146/annurev.pu.03.050182.000505 6293517
    [Google Scholar]
  4. Youlden D.R. Cramb S.M. Dunn N.A.M. Muller J.M. Pyke C.M. Baade P.D. The descriptive epidemiology of female breast cancer: An international comparison of screening, incidence, survival and mortality. Cancer Epidemiol. 2012 36 3 237 248 10.1016/j.canep.2012.02.007 22459198
    [Google Scholar]
  5. Augustine D. Khan W. Rao R. Patil S. Awan K. Sowmya S. Haragannavar V. Prasad K. Lipid metabolism in cancer: A systematic review. J. Carcinog. 2021 20 1 4 10.4103/jcar.JCar_15_20 34321955
    [Google Scholar]
  6. Torre L.A. Bray F. Siegel R.L. Ferlay J. Lortet-Tieulent J. Jemal A. Global cancer statistics, 2012. CA Cancer J. Clin. 2015 65 2 87 108 10.3322/caac.21262 25651787
    [Google Scholar]
  7. Feinberg A.P. Fallin M.D. Epigenetics at the crossroads of genes and the environment. JAMA 2015 314 11 1129 1130 10.1001/jama.2015.10414 26372577
    [Google Scholar]
  8. Butler L.M. Perone Y. Dehairs J. Lupien L.E. de Laat V. Talebi A. Loda M. Kinlaw W.B. Swinnen J.V. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv. Drug Deliv. Rev. 2020 159 245 293 10.1016/j.addr.2020.07.013 32711004
    [Google Scholar]
  9. Swinnen J.V. Brusselmans K. Verhoeven G. Increased lipogenesis in cancer cells: New players, novel targets. Curr. Opin. Clin. Nutr. Metab. Care 2006 9 4 358 365 10.1097/01.mco.0000232894.28674.30 16778563
    [Google Scholar]
  10. Warburg O. Wind F. Negelein E. The metabolism of tumors in the body. J. Gen. Physiol. 1927 8 6 519 530 10.1085/jgp.8.6.519 19872213
    [Google Scholar]
  11. Baenke F. Peck B. Miess H. Schulze A. Hooked on fat: The role of lipid synthesis in cancer metabolism and tumour development. Dis. Model. Mech. 2013 6 6 1353 1363 10.1242/dmm.011338 24203995
    [Google Scholar]
  12. Huang C. Freter C. Lipid metabolism, apoptosis and cancer therapy. Int. J. Mol. Sci. 2015 16 1 924 949 10.3390/ijms16010924 25561239
    [Google Scholar]
  13. Li L. Han J. Wang Z. Liu J. Wei J. Xiong S. Zhao Z. Mass spectrometry methodology in lipid analysis. Int. J. Mol. Sci. 2014 15 6 10492 10507 10.3390/ijms150610492 24921707
    [Google Scholar]
  14. Lydic T.A. Goo Y.H. Lipidomics unveils the complexity of the lipidome in metabolic diseases. Clin. Transl. Med. 2018 7 1 e4 10.1186/s40169‑018‑0182‑9 29374337
    [Google Scholar]
  15. Hanahan D. Weinberg R.A. Hallmarks of cancer: The next generation. Cell 2011 144 5 646 674 10.1016/j.cell.2011.02.013 21376230
    [Google Scholar]
  16. Long J. Zhang C.J. Zhu N. Du K. Yin Y.F. Tan X. Liao D.F. Qin L. Lipid metabolism and carcinogenesis, cancer development. Am. J. Cancer Res. 2018 8 5 778 791 29888102
    [Google Scholar]
  17. Corsetto P.A. Zava S. Rizzo A.M. Colombo I. The critical impact of sphingolipid metabolism in breast cancer progression and drug response. Int. J. Mol. Sci. 2023 24 3 2107 10.3390/ijms24032107 36768427
    [Google Scholar]
  18. Saddoughi S.A. Song P. Ogretmen B. Roles of bioactive sphingolipids in cancer biology and therapeutics. Subcell. Biochem. 2008 49 413 440 10.1007/978‑1‑4020‑8831‑5_16
    [Google Scholar]
  19. Quinville B.M. Deschenes N.M. Ryckman A.E. Walia J.S. A comprehensive review: Sphingolipid metabolism and implications of disruption in sphingolipid homeostasis. Int. J. Mol. Sci. 2021 22 11 5793 10.3390/ijms22115793 34071409
    [Google Scholar]
  20. Gault C.R. Obeid L.M. Hannun Y.A. An overview of sphingolipid metabolism: From synthesis to breakdown. Adv. Exp. Med. Biol. 2010 688 1 23 10.1007/978‑1‑4419‑6741‑1_1 20919643
    [Google Scholar]
  21. Storozhenko G. Kharchenko V. Krasilnikova O. Tkachenko O. Overview of concepts of the sphingolipid metabolism. Sci. Rise Biol. Sci. 2021 2 27 23 27 10.15587/2519‑8025.2021.234699
    [Google Scholar]
  22. Li R.Z. Wang X.R. Wang J. Xie C. Wang X.X. Pan H.D. Meng W.Y. Liang T.L. Li J.X. Yan P.Y. Wu Q.B. Liu L. Yao X.J. Leung E.L.H. The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance. Front. Oncol. 2022 12 941643 10.3389/fonc.2022.941643 35965565
    [Google Scholar]
  23. Sandhoff K. Neuronal sphingolipidoses: Membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism. Biochimie 2016 130 146 151 10.1016/j.biochi.2016.05.004 27157270
    [Google Scholar]
  24. Gupta P. Taiyab A. Hussain A. Alajmi M.F. Islam A. Hassan M.I. Targeting the sphingosine Kinase/Sphingosine-1-Phosphate signaling axis in drug discovery for cancer therapy. Cancers 2021 13 8 1898 10.3390/cancers13081898 33920887
    [Google Scholar]
  25. Hannun Y.A. Obeid L.M. Principles of bioactive lipid signalling: Lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 2008 9 2 139 150 10.1038/nrm2329 18216770
    [Google Scholar]
  26. Acharya U. Acharya J.K. Enzymes of Sphingolipid metabolism in Drosophila melanogaster. Cell. Mol. Life Sci. 2005 62 2 128 142 10.1007/s00018‑004‑4254‑1 15666085
    [Google Scholar]
  27. Hanada K. Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2003 1632 1-3 16 30 10.1016/S1388‑1981(03)00059‑3 12782147
    [Google Scholar]
  28. Hanada K. Kumagai K. Tomishige N. Yamaji T. CERT-mediated trafficking of ceramide. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2009 1791 7 684 691 10.1016/j.bbalip.2009.01.006 19416656
    [Google Scholar]
  29. Zeidan Y.H. Hannun Y.A. Translational aspects of sphingolipid metabolism. Trends Mol. Med. 2007 13 8 327 336 10.1016/j.molmed.2007.06.002 17588815
    [Google Scholar]
  30. Pralhada Rao R. Vaidyanathan N. Rengasamy M. Mammen Oommen A. Somaiya N. Jagannath M.R. Sphingolipid metabolic pathway: An overview of major roles played in human diseases. J. Lipids 2013 2013 1 12 10.1155/2013/178910 23984075
    [Google Scholar]
  31. Kolter T. Sandhoff K. Principles of lysosomal membrane digestion: Stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids. Annu. Rev. Cell Dev. Biol. 2005 21 1 81 103 10.1146/annurev.cellbio.21.122303.120013 16212488
    [Google Scholar]
  32. Funato K. Riezman H. Vesicular and nonvesicular transport of ceramide from ER to the Golgi apparatus in yeast. J. Cell Biol. 2001 155 6 949 960 10.1083/jcb.200105033 11733544
    [Google Scholar]
  33. Hanada K. Kumagai K. Yasuda S. Miura Y. Kawano M. Fukasawa M. Nishijima M. Molecular machinery for non-vesicular trafficking of ceramide. Nature 2003 426 6968 803 809 10.1038/nature02188 14685229
    [Google Scholar]
  34. Merrill A.H. Sandhoff K. Sphingolipids: Metabolism and cell signaling. New Comprehensive Biochemistry Elsevier 2002 36 373 407 10.1016/S0167‑7306(02)36016‑2
    [Google Scholar]
  35. Kramer R. Bielawski J. Kistner-Griffin E. Othman A. Alecu I. Ernst D. Kornhauser Hornemann T. Spassieva S. Neurotoxic 1‐deoxysphingolipids and paclitaxel‐induced peripheral neuropathy. FASEB J. 2015 29 11 4461 4472 10.1096/fj.15‑272567 26198449
    [Google Scholar]
  36. Becker K.A. Uerschels A.K. Goins L. Doolen S. McQuerry K.J. Bielawski J. Sure U. Bieberich E. Taylor B.K. Gulbins E. Spassieva S.D. Role of 1‐Deoxysphingolipids in docetaxel neurotoxicity. J. Neurochem. 2020 154 6 662 672 10.1111/jnc.14985 32058598
    [Google Scholar]
  37. Bode H. Bourquin F. Suriyanarayanan S. Wei Y. Alecu I. Othman A. Von Eckardstein A. Hornemann T. HSAN1 mutations in serine palmitoyltransferase reveal a close structure–function–phenotype relationship. Hum. Mol. Genet. 2016 25 5 853 865 10.1093/hmg/ddv611 26681808
    [Google Scholar]
  38. Han G. Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities. Proc. Natl. Acad. Sci. U.S.A. 2009 106 20 8186 8191 10.1073/pnas.0905301106
    [Google Scholar]
  39. Siow D.L. Wattenberg B.W. Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis. J. Biol. Chem. 2012 287 48 40198 40204 10.1074/jbc.C112.404012 23066021
    [Google Scholar]
  40. Breslow D.K. Collins S.R. Bodenmiller B. Aebersold R. Simons K. Shevchenko A. Ejsing C.S. Weissman J.S. Orm family proteins mediate sphingolipid homeostasis. Nature 2010 463 7284 1048 1053 10.1038/nature08787 20182505
    [Google Scholar]
  41. Mu J. Lam S.M. Shui G. Emerging roles and therapeutic potentials of sphingolipids in pathophysiology: Emphasis on fatty acyl heterogeneity. J. Genet. Genomics 2023 51 3 268 278 10.1016/j.jgg.2023.06.006 37364711
    [Google Scholar]
  42. Montavoci L. Romano D. Colombo L. Zulueta A. Cas M.D. Scavone M. Tosi D. Bernardelli C. Autelitano A. Trinchera M. Rossetti L. Caretti A. Use of Myriocin as co-adjuvant in glaucoma surgery: An in vitro study. Int. J. Biochem. Cell Biol. 2024 177 106699 10.1016/j.biocel.2024.106699 39571676
    [Google Scholar]
  43. Jang H. Ojha U. Jeong J.H. Park K.G. Lee S.Y. Lee Y.M. Myriocin suppresses tumor growth by modulating macrophage polarization and function through the PI3K/Akt/mTOR pathway. Arch. Pharm. Res. 2023 46 7 629 645 10.1007/s12272‑023‑01454‑1 37468765
    [Google Scholar]
  44. Thomas R.J. Oleinik N. Panneer Selvam S. Vaena S.G. Dany M. Nganga R.N. Depalma R. Baron K.D. Kim J. Szulc Z.M. Ogretmen B. HPV /E7 induces chemotherapy‐mediated tumor suppression by ceramide‐dependent mitophagy. EMBO Mol. Med. 2017 9 8 1030 1051 10.15252/emmm.201607088 28606997
    [Google Scholar]
  45. Ghanbari Movahed Z. Rastegari-Pouyani M. Mohammadi M. Mansouri K. Cancer cells change their glucose metabolism to overcome increased ROS: One step from cancer cell to cancer stem cell? Biomed. Pharmacother. 2019 112 108690 10.1016/j.biopha.2019.108690 30798124
    [Google Scholar]
  46. Park W.J. Brenner O. Kogot-Levin A. Saada A. Merrill A.H. Jr Pewzner-Jung Y. Futerman A.H. Development of pheochromocytoma in ceramide synthase 2 null mice. Endocr. Relat. Cancer 2015 22 4 623 632 10.1530/ERC‑15‑0058 26113602
    [Google Scholar]
  47. Fekry B. Jeffries K.A. Esmaeilniakooshkghazi A. Ogretmen B. Krupenko S.A. Krupenko N.I. CerS6 is a novel transcriptional target of p53 protein activated by non-genotoxic stress. J. Biol. Chem. 2016 291 32 16586 16596 10.1074/jbc.M116.716902 27302066
    [Google Scholar]
  48. White-Gilbertson S. Mullen T. Senkal C. Lu P. Ogretmen B. Obeid L. Voelkel-Johnson C. Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells. Oncogene 2009 28 8 1132 1141 10.1038/onc.2008.468 19137010
    [Google Scholar]
  49. Meyers-Needham M. Ponnusamy S. Gencer S. Jiang W. Thomas R.J. Senkal C.E. Ogretmen B. Concerted functions of HDAC1 and microRNA‐574‐5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells. EMBO Mol. Med. 2012 4 2 78 92 10.1002/emmm.201100189 22180294
    [Google Scholar]
  50. Loiseau N. Polizzi A. Dupuy A. Therville N. Rakotonirainy M. Loy J. Viadere J.L. Cossalter A.M. Bailly J.D. Puel O. Kolf-Clauw M. Bertrand-Michel J. Levade T. Guillou H. Oswald I.P. New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver. Arch. Toxicol. 2015 89 9 1619 1629 10.1007/s00204‑014‑1323‑6 25155190
    [Google Scholar]
  51. Rahmaniyan M. Curley R.W. Jr Obeid L.M. Hannun Y.A. Kraveka J.M. Identification of dihydroceramide desaturase as a direct in vitro target for fenretinide. J. Biol. Chem. 2011 286 28 24754 24764 10.1074/jbc.M111.250779 21543327
    [Google Scholar]
  52. Orienti I. Francescangeli F. De Angelis M.L. Fecchi K. Bongiorno-Borbone L. Signore M. Peschiaroli A. Boe A. Bruselles A. Costantino A. Eramo A. Salvati V. Sette G. Contavalli P. Zolla L. Oki T. Kitamura T. Spada M. Giuliani A. Baiocchi M. La Torre F. Melino G. Tartaglia M. De Maria R. Zeuner A. A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors. Cell Death Dis. 2019 10 7 529 10.1038/s41419‑019‑1775‑y 31332161
    [Google Scholar]
  53. Airola M.V. Shanbhogue P. Shamseddine A.A. Guja K.E. Senkal C.E. Maini R. Bartke N. Wu B.X. Obeid L.M. Garcia-Diaz M. Hannun Y.A. Structure of human nSMase2 reveals an interdomain allosteric activation mechanism for ceramide generation. Proc. Natl. Acad. Sci. USA 2017 114 28 E5549 E5558 10.1073/pnas.1705134114 28652336
    [Google Scholar]
  54. Gorelik A. Illes K. Heinz L.X. Superti-Furga G. Nagar B. Crystal structure of mammalian acid sphingomyelinase. Nat. Commun. 2016 7 1 12196 10.1038/ncomms12196 27435900
    [Google Scholar]
  55. Santana P. Peña L.A. Haimovitz-Friedman A. Martin S. Green D. McLoughlin M. Cordon-Cardo C. Schuchman E.H. Fuks Z. Kolesnick R. Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell 1996 86 2 189 199 10.1016/S0092‑8674(00)80091‑4 8706124
    [Google Scholar]
  56. Laddu A.R. Somani P. Desipramine toxicity and its treatment. Toxicol. Appl. Pharmacol. 1969 15 2 287 294 10.1016/0041‑008X(69)90029‑5 5804746
    [Google Scholar]
  57. Degagné E. Pandurangan A. Bandhuvula P. Kumar A. Eltanawy A. Zhang M. Yoshinaga Y. Nefedov M. de Jong P.J. Fong L.G. Young S.G. Bittman R. Ahmedi Y. Saba J.D. Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs. J. Clin. Invest. 2014 124 12 5368 5384 10.1172/JCI74188 25347472
    [Google Scholar]
  58. Ogretmen B. Sphingolipid metabolism in cancer signalling and therapy. Nat. Rev. Cancer 2018 18 1 33 50 10.1038/nrc.2017.96 29147025
    [Google Scholar]
  59. Furuya H. Shimizu Y. Kawamori T. Sphingolipids in cancer. Cancer Metastasis Rev. 2011 30 3-4 567 576 10.1007/s10555‑011‑9304‑1 22005951
    [Google Scholar]
  60. Fu Y. Zou T. Shen X. Nelson P.J. Li J. Wu C. Yang J. Zheng Y. Bruns C. Zhao Y. Qin L. Dong Q. Lipid metabolism in cancer progression and therapeutic strategies. MedComm 2021 2 1 27 59 10.1002/mco2.27 34766135
    [Google Scholar]
  61. Morigny P. Zuber J. Haid M. Kaltenecker D. Riols F. Lima J.D.C. Simoes E. Otoch J.P. Schmidt S.F. Herzig S. Adamski J. Seelaender M. Berriel Diaz M. Rohm M. High levels of modified ceramides are a defining feature of murine and human cancer cachexia. J. Cachexia Sarcopenia Muscle 2020 11 6 1459 1475 10.1002/jcsm.12626 33090732
    [Google Scholar]
  62. Wang S. Liang Y. Chang W. Hu B. Zhang Y. Triple negative breast cancer depends on sphingosine kinase 1 (Sphk1)/sphingosine- 1-phosphate (s1p)/sphingosine 1-phosphate receptor 3 (s1pr3)/notch signaling for metastasis. Med. Sci. Monit. 2018 24 1912 1923 10.12659/MSM.905833 29605826
    [Google Scholar]
  63. Hait N.C. Maiti A. The role of sphingosine-1-phosphate and ceramide-1-phosphate in inflammation and cancer. Mediators Inflamm. 2017 2017 1 17 10.1155/2017/4806541 29269995
    [Google Scholar]
  64. Alshaker H. Thrower H. Pchejetski D. Sphingosine kinase 1 in breast cancer-A new molecular marker and a therapy target. Front Oncol 2020 10 289 10.3389/fonc.2020.00289
    [Google Scholar]
  65. Zhang L. Wang X. Bullock A.J. Callea M. Shah H. Song J. Moreno K. Visentin B. Deutschman D. Alsop D.C. Atkins M.B. Mier J.W. Signoretti S. Bhasin M. Sabbadini R.A. Bhatt R.S. Anti-S1P antibody as a novel therapeutic strategy for VEGFR TKI-resistant renal cancer. Clin. Cancer Res. 2015 21 8 1925 1934 10.1158/1078‑0432.CCR‑14‑2031 25589614
    [Google Scholar]
  66. Terzić J. Grivennikov S. Karin E. Karin M. Inflammation and colon cancer. Gastroenterology 2010 138 6 2101 2114.e5 10.1053/j.gastro.2010.01.058 20420949
    [Google Scholar]
  67. Nagahashi M. Takabe K. Terracina K.P. Soma D. Hirose Y. Kobayashi T. Matsuda Y. Wakai T. Sphingosine-1-phosphate transporters as targets for cancer therapy. BioMed Res. Int. 2014 2014 1 7 10.1155/2014/651727 25133174
    [Google Scholar]
  68. Takabe K. Paugh S.W. Milstien S. Spiegel S. “Inside-out” signaling of sphingosine-1-phosphate: therapeutic targets. Pharmacol. Rev. 2008 60 2 181 195 10.1124/pr.107.07113 18552276
    [Google Scholar]
  69. Wang P. Yuan Y. Lin W. Zhong H. Xu K. Qi X. Roles of sphingosine-1-phosphate signaling in cancer. Cancer Cell Int. 2019 19 1 295 10.1186/s12935‑019‑1014‑8 31807117
    [Google Scholar]
  70. Strub G.M. Maceyka M. Hait N.C. Milstien S. Spiegel S. Extracellular and intracellular actions of sphingosine-1-phosphate. Adv. Exp. Med. Biol. 2010 688 141 155 10.1007/978‑1‑4419‑6741‑1_10 20919652
    [Google Scholar]
  71. Maceyka M. Sankala H. Hait N.C. Le Stunff H. Liu H. Toman R. Collier C. Zhang M. Satin L.S. Merrill A.H. Jr Milstien S. Spiegel S. SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism. J. Biol. Chem. 2005 280 44 37118 37129 10.1074/jbc.M502207200 16118219
    [Google Scholar]
  72. Takabe K. Kim R.H. Allegood J.C. Mitra P. Ramachandran S. Nagahashi M. Harikumar K.B. Hait N.C. Milstien S. Spiegel S. Estradiol induces export of sphingosine 1-phosphate from breast cancer cells via ABCC1 and ABCG2. J. Biol. Chem. 2010 285 14 10477 10486 10.1074/jbc.M109.064162 20110355
    [Google Scholar]
  73. Takabe K. Spiegel S. Export of sphingosine-1-phosphate and cancer progression. J. Lipid Res. 2014 55 9 1839 1846 10.1194/jlr.R046656 24474820
    [Google Scholar]
  74. Surh Y.-J. Abstract ED01-01: Targeting inflammatory microenvironment for cancer chemoprevention and therapy. Cancer Prev Res 2013 6 suppl. 11 ED01-01 10.1158/1940‑6215.PREV‑13‑ED01‑01
    [Google Scholar]
  75. Hanyu T. Nagahashi M. Ichikawa H. Ishikawa T. Kobayashi T. Wakai T. Expression of phosphorylated sphingosine kinase 1 is associated with diffuse type and lymphatic invasion in human gastric cancer. Surgery 2018 163 6 1301 1306 10.1016/j.surg.2017.11.024 29370930
    [Google Scholar]
  76. Nagahashi M. Yamada A. Katsuta E. Aoyagi T. Huang W.C. Terracina K.P. Hait N.C. Allegood J.C. Tsuchida J. Yuza K. Nakajima M. Abe M. Sakimura K. Milstien S. Wakai T. Spiegel S. Takabe K. Targeting the SphK1/S1P/S1PR1 axis that links obesity, chronic inflammation, and breast cancer metastasis. Cancer Res. 2018 78 7 1713 1725 10.1158/0008‑5472.CAN‑17‑1423 29351902
    [Google Scholar]
  77. Hait N.C. Allegood J. Maceyka M. Strub G.M. Harikumar K.B. Singh S.K. Luo C. Marmorstein R. Kordula T. Milstien S. Spiegel S. Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate. Science 2009 325 5945 1254 1257 10.1126/science.1176709 19729656
    [Google Scholar]
  78. Alvarez S.E. Harikumar K.B. Hait N.C. Allegood J. Strub G.M. Kim E.Y. Maceyka M. Jiang H. Luo C. Kordula T. Milstien S. Spiegel S. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature 2010 465 7301 1084 1088 10.1038/nature09128 20577214
    [Google Scholar]
  79. Nagahashi M. Takabe K. Liu R. Peng K. Wang X. Wang Y. Hait N.C. Wang X. Allegood J.C. Yamada A. Aoyagi T. Liang J. Pandak W.M. Spiegel S. Hylemon P.B. Zhou H. Conjugated bile acid–activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression. Hepatology 2015 61 4 1216 1226 10.1002/hep.27592 25363242
    [Google Scholar]
  80. Hait N.C. Wise L.E. Allegood J.C. O’Brien M. Avni D. Reeves T.M. Knapp P.E. Lu J. Luo C. Miles M.F. Milstien S. Lichtman A.H. Spiegel S. Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory. Nat. Neurosci. 2014 17 7 971 980 10.1038/nn.3728 24859201
    [Google Scholar]
  81. Jin L. Liu W.R. Tian M.X. Fan J. Shi Y.H. The SphKs/S1P/S1PR1 axis in immunity and cancer: More ore to be mined. World J. Surg. Oncol. 2016 14 1 131 10.1186/s12957‑016‑0884‑7 27129720
    [Google Scholar]
  82. Olivera A. Mizugishi K. Tikhonova A. Ciaccia L. Odom S. Proia R.L. Rivera J. The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Immunity 2007 26 3 287 297 10.1016/j.immuni.2007.02.008 17346996
    [Google Scholar]
  83. Mendelson K. Zygmunt T. Torres-Vázquez J. Evans T. Hla T. Sphingosine 1-phosphate receptor signaling regulates proper embryonic vascular patterning. J. Biol. Chem. 2013 288 4 2143 2156 10.1074/jbc.M112.427344 23229546
    [Google Scholar]
  84. Kawahara A. Nishi T. Hisano Y. Fukui H. Yamaguchi A. Mochizuki N. The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors. Science 2009 323 5913 524 527 10.1126/science.1167449 19074308
    [Google Scholar]
  85. Osborne N. Brand-Arzamendi K. Ober E.A. Jin S.W. Verkade H. Holtzman N.G. Yelon D. Stainier D.Y.R. The spinster homolog, two of hearts, is required for sphingosine 1-phosphate signaling in zebrafish. Curr. Biol. 2008 18 23 1882 1888 10.1016/j.cub.2008.10.061 19062281
    [Google Scholar]
  86. Moro K. Kawaguchi T. Tsuchida J. Gabriel E. Qi Q. Yan L. Wakai T. Takabe K. Nagahashi M. Ceramide species are elevated in human breast cancer and are associated with less aggressiveness. Oncotarget 2018 9 28 19874 19890 10.18632/oncotarget.24903 29731990
    [Google Scholar]
  87. Neubauer H.A. Pitson S.M. Roles, regulation and inhibitors of sphingosine kinase 2. FEBS J. 2013 280 21 5317 5336 10.1111/febs.12314
    [Google Scholar]
  88. Sobue S. Iwasaki T. Sugisaki C. Nagata K. Kikuchi R. Murakami M. Takagi A. Kojima T. Banno Y. Akao Y. Nozawa Y. Kannagi R. Suzuki M. Abe A. Naoe T. Murate T. Quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia and myelodysplastic syndromes. Leukemia 2006 20 11 2042 2046 10.1038/sj.leu.2404386 16990773
    [Google Scholar]
  89. Ruckhäberle E. Rody A. Engels K. Gaetje R. von Minckwitz G. Schiffmann S. Grösch S. Geisslinger G. Holtrich U. Karn T. Kaufmann M. Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res. Treat. 2008 112 1 41 52 10.1007/s10549‑007‑9836‑9 18058224
    [Google Scholar]
  90. Sutphen R. Xu Y. Wilbanks G.D. Fiorica J. Grendys E.C. Jr LaPolla J.P. Arango H. Hoffman M.S. Martino M. Wakeley K. Griffin D. Blanco R.W. Cantor A.B. Xiao Y. Krischer J.P. Lysophospholipids are potential biomarkers of ovarian cancer. Cancer Epidemiol. Biomarkers Prev. 2004 13 7 1185 1191 10.1158/1055‑9965.1185.13.7 15247129
    [Google Scholar]
  91. Hong G. Baudhuin L.M. Xu Y. Sphingosine‐1‐phosphate modulates growth and adhesion of ovarian cancer cells. FEBS Lett. 1999 460 3 513 518 10.1016/S0014‑5793(99)01400‑3 10556527
    [Google Scholar]
  92. Alvarez S.E. Milstien S. Spiegel S. Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol. Metab. 2007 18 8 300 307 10.1016/j.tem.2007.07.005 17904858
    [Google Scholar]
  93. Pitson S.M. Moretti P.A. Zebol J.R. Lynn H.E. Xia P. Vadas M.A. Wattenberg B.W. Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation. EMBO J. 2003 22 20 5491 5500 10.1093/emboj/cdg540 14532121
    [Google Scholar]
  94. Hobson J.P. Rosenfeldt H.M. Barak L.S. Olivera A. Poulton S. Caron M.G. Milstien S. Spiegel S. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science 2001 291 5509 1800 1803 10.1126/science.1057559 11230698
    [Google Scholar]
  95. Stahelin R.V. Hwang J.H. Kim J.H. Park Z.Y. Johnson K.R. Obeid L.M. Cho W. The mechanism of membrane targeting of human sphingosine kinase 1. J. Biol. Chem. 2005 280 52 43030 43038 10.1074/jbc.M507574200 16243846
    [Google Scholar]
  96. Pitson S.M. Xia P. Leclercq T.M. Moretti P.A.B. Zebol J.R. Lynn H.E. Wattenberg B.W. Vadas M.A. Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling. J. Exp. Med. 2005 201 1 49 54 10.1084/jem.20040559 15623571
    [Google Scholar]
  97. Döll F. Pfeilschifter J. Huwiler A. 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. Lipids 2005 1738 1-3 72 81 10.1016/j.bbalip.2005.12.001 16414307
    [Google Scholar]
  98. Shida D. Takabe K. Kapitonov D. Milstien S. Spiegel S. Targeting SphK1 as a new strategy against cancer. Curr. Drug Targets 2008 9 8 662 673 10.2174/138945008785132402 18691013
    [Google Scholar]
  99. Pulkoski-Gross M.J. Obeid L.M. Molecular mechanisms of regulation of sphingosine kinase 1. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2018 1863 11 1413 1422 10.1016/j.bbalip.2018.08.015 30591148
    [Google Scholar]
  100. Nicholas S.E. Rowsey T.G. Priyadarsini S. Mandal N.A. Karamichos D. Unravelling the interplay of sphingolipids and TGF-β signaling in the human corneal stroma. PLoS One 2017 12 8 e0182390 10.1371/journal.pone.0182390 28806736
    [Google Scholar]
  101. Hatoum D. Haddadi N. Lin Y. Nassif N.T. McGowan E.M. Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: Challenges for SphK as an oncotarget. Oncotarget 2017 8 22 36898 36929 10.18632/oncotarget.16370 28415564
    [Google Scholar]
  102. Paul B. Lewinska M. Andersen J.B. Lipid alterations in chronic liver disease and liver cancer. JHEP Reports 2022 4 6 100479 10.1016/j.jhepr.2022.100479 35469167
    [Google Scholar]
  103. Hart P.C. Chiyoda T. Liu X. Weigert M. Curtis M. Chiang C.Y. Loth R. Lastra R. McGregor S.M. Locasale J.W. Lengyel E. Romero I.L. SPHK1 is a novel target of metformin in ovarian cancer. Mol. Cancer Res. 2019 17 4 870 881 10.1158/1541‑7786.MCR‑18‑0409 30655321
    [Google Scholar]
  104. Ding X. Zhang Y. Huang T. Xu G. Peng C. Chen G. Kong B. Friess H. Shen S. Lv Y. Roberts L.R. Wang L. Zou X. 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. 2019 9 3 546 561 30949409
    [Google Scholar]
  105. Cannavo A. Liccardo D. Komici K. Corbi G. de Lucia C. Femminella G.D. Elia A. Bencivenga L. Ferrara N. Koch W.J. Paolocci N. Rengo G. Sphingosine kinases and sphingosine 1-phosphate receptors: Signaling and actions in the cardiovascular system. Front. Pharmacol. 2017 8 AUG 556 10.3389/fphar.2017.00556 28878674
    [Google Scholar]
  106. Hasanifard L. Sheervalilou R. Majidinia M. Yousefi B. New insights into the roles and regulation of SphK2 as a therapeutic target in cancer chemoresistance. J. Cell. Physiol. 2019 234 6 8162 8181 10.1002/jcp.27612 30456838
    [Google Scholar]
  107. Xu D. Zhu H. Wang C. Zhao W. Liu G. Bao G. Cui D. Fan J. Wang F. Jin H. Cui Z. SphK2 over-expression promotes osteosarcoma cell growth. Oncotarget 2017 8 62 105525 105535 10.18632/oncotarget.22314 29285269
    [Google Scholar]
  108. Panneer Selvam S. De Palma R.M. Oaks J.J. Oleinik N. Peterson Y.K. Stahelin R.V. Skordalakes E. Ponnusamy S. Garrett-Mayer E. Smith C.D. Ogretmen B. Binding of the sphingolipid S1P to hTERT stabilizes telomerase at the nuclear periphery by allosterically mimicking protein phosphorylation. Sci. Signal. 2015 8 381 ra58 10.1126/scisignal.aaa4998 26082434
    [Google Scholar]
  109. Strub G.M. Paillard M. Liang J. Gomez L. Allegood J.C. Hait N.C. Maceyka M. Price M.M. Chen Q. Simpson D.C. Kordula T. Milstien S. Lesnefsky E.J. Spiegel S. Sphingosine‐1‐phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration. FASEB J. 2011 25 2 600 612 10.1096/fj.10‑167502 20959514
    [Google Scholar]
  110. Newton J. Lima S. Maceyka M. Spiegel S. Revisiting the sphingolipid rheostat: Evolving concepts in cancer therapy. Exp. Cell Res. 2015 333 2 195 200 10.1016/j.yexcr.2015.02.025 25770011
    [Google Scholar]
  111. Galadari S. Rahman A. Pallichankandy S. Thayyullathil F. Tumor suppressive functions of ceramide: Evidence and mechanisms. Apoptosis 2015 20 5 689 711 10.1007/s10495‑015‑1109‑1 25702155
    [Google Scholar]
  112. Young M.M. Kester M. Wang H.G. Sphingolipids: Regulators of crosstalk between apoptosis and autophagy. J. Lipid Res. 2013 54 1 5 19 10.1194/jlr.R031278 23152582
    [Google Scholar]
  113. Ramanathan R. Olex A.L. Dozmorov M. Bear H.D. Fernandez L.J. Takabe K. Angiopoietin pathway gene expression associated with poor breast cancer survival. Breast Cancer Res. Treat. 2017 162 1 191 198 10.1007/s10549‑017‑4102‑2 28062977
    [Google Scholar]
  114. Al-Rashed F. Ahmad Z. Snider A.J. Thomas R. Kochumon S. Melhem M. Sindhu S. Obeid L.M. Al-Mulla F. Hannun Y.A. Ahmad R. Ceramide kinase regulates TNF-α-induced immune responses in human monocytic cells. Sci. Rep. 2021 11 1 8259 10.1038/s41598‑021‑87795‑7 33859296
    [Google Scholar]
  115. Mitsutake S. Kim T.J. Inagaki Y. Kato M. Yamashita T. Igarashi Y. Ceramide kinase is a mediator of calcium-dependent degranulation in mast cells. J. Biol. Chem. 2004 279 17 17570 17577 10.1074/jbc.M312885200 14769792
    [Google Scholar]
  116. Zhu S. Xu Y. Wang L. Liao S. Wang Y. Shi M. Tu Y. Zhou Y. Wei W. 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. 2021 21 1 42 10.1186/s12935‑020‑01735‑5 33430896
    [Google Scholar]
  117. Schwalm S. Erhardt M. Römer I. Pfeilschifter J. Zangemeister-Wittke U. Huwiler A. 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. 2020 21 4 1396 10.3390/ijms21041396 32092937
    [Google Scholar]
  118. Gomez-Larrauri A. Das Adhikari U. Aramburu-Nuñez M. Custodia A. Ouro A. Ceramide metabolism enzymes-therapeutic targets against cancer. Medicina 2021 57 7 729 10.3390/medicina57070729
    [Google Scholar]
  119. Payne A.W. Pant D.K. Pan T.C. Chodosh L.A. Ceramide kinase promotes tumor cell survival and mammary tumor recurrence. Cancer Res. 2014 74 21 6352 6363 10.1158/0008‑5472.CAN‑14‑1292 25164007
    [Google Scholar]
  120. Camacho L. Ouro A. Gomez-Larrauri A. Carracedo A. Gomez-Muñoz A. Implication of ceramide kinase/C1P in cancer development and progression. Cancers 2022 14 1 227 10.3390/cancers14010227 35008391
    [Google Scholar]
  121. Pierucci F. Frati A. Battistini C. Penna F. Costelli P. Meacci E. Control of skeletal muscle atrophy associated to cancer or corticosteroids by ceramide kinase. Cancers 2021 13 13 3285 10.3390/cancers13133285 34209043
    [Google Scholar]
  122. Gómez-Muñoz A. Kong J.Y. Salh B. Steinbrecher U.P. Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase in macrophages. J. Lipid Res. 2004 45 1 99 105 10.1194/jlr.M300158‑JLR200 14523050
    [Google Scholar]
  123. Gomez-Larrauri A. Ouro A. Trueba M. Gomez-Muñoz A. Regulation of cell growth, survival and migration by ceramide 1-phosphate - Implications in lung cancer progression and inflammation. Cell. Signal. 2021 83 109980 10.1016/j.cellsig.2021.109980 33727076
    [Google Scholar]
  124. Vincent A. Herman J. Schulick R. Hruban R.H. Goggins M. Pancreatic cancer. Lancet 2011 378 9791 607 620 10.1016/S0140‑6736(10)62307‑0 21620466
    [Google Scholar]
  125. Rivera I.G. Ordoñez M. Presa N. Gangoiti P. Gomez-Larrauri A. Trueba M. Fox T. Kester M. Gomez-Muñoz A. Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells. Biochem. Pharmacol. 2016 102 107 119 10.1016/j.bcp.2015.12.009 26707801
    [Google Scholar]
  126. Camacho L. Zabala-Letona A. Cortazar A.R. Astobiza I. Dominguez-Herrera A. Ercilla A. Crespo J. Viera C. Fernández-Ruiz S. Martinez-Gonzalez A. Torrano V. Martín-Martín N. Gomez-Muñoz A. Carracedo A. Identification of androgen receptor metabolic correlome reveals the repression of ceramide kinase by androgens. Cancers 2021 13 17 4307 10.3390/cancers13174307 34503116
    [Google Scholar]
  127. Wu L. Runkle C. Jin H-J. Yu J. Li J. Yang X. Kuzel T. Lee C. Yu J. CCN3/NOV gene expression in human prostate cancer is directly suppressed by the androgen receptor. Oncogene 2014 33 4 504 513 10.1038/onc.2012.602 23318417
    [Google Scholar]
  128. Bhadwal P. Dahiya D. Shinde D. Vaiphei K. Math R.G.H. Randhawa V. Agnihotri N. LC-HRMS based approach to identify novel sphingolipid biomarkers in breast cancer patients. Sci. Rep. 2020 10 1 4668 10.1038/s41598‑020‑61283‑w 32170160
    [Google Scholar]
  129. Rajput K. Ansari M.N. Jha S.K. Pani T. Medatwal N. Chattopadhyay S. Bajaj A. Dasgupta U. Ceramide kinase (CERK) emerges as a common therapeutic target for triple positive and triple negative breast cancer cells. Cancers 2022 14 18 4496 10.3390/cancers14184496 36139656
    [Google Scholar]
  130. Mitra P. Maceyka M. Payne S.G. Lamour N. Milstien S. Chalfant C.E. Spiegel S. Ceramide kinase regulates growth and survival of A549 human lung adenocarcinoma cells. FEBS Lett. 2007 581 4 735 740 10.1016/j.febslet.2007.01.041 17274985
    [Google Scholar]
  131. Nunes J. Naymark M. Sauer L. Muhammad A. Keun H. Sturge J. Stebbing J. Waxman J. Pchejetski D. Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection. Br. J. Cancer 2012 106 5 909 915 10.1038/bjc.2012.14 22315056
    [Google Scholar]
  132. Sedić M. Grbčić P. Pavelić S.K. Bioactive sphingolipids as biomarkers predictive of disease severity and treatment response in cancer: Current status and translational challenges. Anticancer Res. 2019 39 1 41 56 10.21873/anticanres.13078 30591439
    [Google Scholar]
  133. Malavaud B. Pchejetski D. Mazerolles C. de Paiva G.R. Calvet C. Doumerc N. Pitson S. Rischmann P. Cuvillier O. Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens. Eur. J. Cancer 2010 46 18 3417 3424 10.1016/j.ejca.2010.07.053 20970322
    [Google Scholar]
  134. Waller L.P. Deshpande V. Pyrsopoulos N. Hepatocellular carcinoma: A comprehensive review. World J. Hepatol. 2015 7 26 2648 2663 10.4254/wjh.v7.i26.2648 26609342
    [Google Scholar]
  135. Uranbileg B. Ikeda H. Kurano M. Enooku K. Sato M. Saigusa D. Aoki J. Ishizawa T. Hasegawa K. Kokudo N. Yatomi Y. 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 One 2016 11 2 e0149462 10.1371/journal.pone.0149462 26886371
    [Google Scholar]
  136. Cai H. Xie X. Ji L. Ruan X. Zheng Z. Sphingosine kinase 1: A novel independent prognosis biomarker in hepatocellular carcinoma. Oncol. Lett. 2017 13 4 2316 2322 10.3892/ol.2017.5732 28454397
    [Google Scholar]
  137. Fitian A.I. Nelson D.R. Liu C. Xu Y. Ararat M. Cabrera R. Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC / MS and UPLC / MS ‐ MS. Liver Int. 2014 34 9 1428 1444 10.1111/liv.12541 24661807
    [Google Scholar]
  138. Grammatikos G. Schoell N. Ferreirós N. Bon D. Herrmann E. Farnik H. Köberle V. Piiper A. Zeuzem S. Kronenberger B. Waidmann O. Pfeilschifter J. Serum sphingolipidomic analyses reveal an upregulation of C16- ceramide and sphingosine-1-phosphate in hepatocellular carcinoma. Oncotarget 2016 7 14 18095 18105 10.18632/oncotarget.7741 26933996
    [Google Scholar]
  139. Krautbauer S. Meier E.M. Rein-Fischboeck L. Pohl R. Weiss T.S. Sigruener A. Aslanidis C. Liebisch G. Buechler C. Ceramide and polyunsaturated phospholipids are strongly reduced in human hepatocellular carcinoma. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2016 1861 11 1767 1774 10.1016/j.bbalip.2016.08.014 27570113
    [Google Scholar]
  140. Krautbauer S. Weiss T.S. Wiest R. Schacherer D. Liebisch G. Buechler C. Diagnostic value of systemic cholesteryl ester/free cholesterol ratio in hepatocellular carcinoma. Anticancer Res. 2017 37 7 3527 3535 10.21873/anticanres.11721 28668842
    [Google Scholar]
  141. Tholey R. Sawicki J.A. Brody J.R. Molecular-based and alternative therapies for pancreatic cancer: Looking “out of the box”. Cancer J. 2012 18 6 665 673 10.1097/PPO.0b013e3182793ff6 23187855
    [Google Scholar]
  142. Jiang Y. DiVittore N. Young M. Jia Z. Xie K. Ritty T. Kester M. Fox T. Altered sphingolipid metabolism in patients with metastatic pancreatic cancer. Biomolecules 2013 3 3 435 448 10.3390/biom3030435 24970174
    [Google Scholar]
  143. Di Gangi I.M. Mazza T. Fontana A. Copetti M. Fusilli C. Ippolito A. Mattivi F. Latiano A. Andriulli A. Vrhovsek U. Pazienza V. Metabolomic profile in pancreatic cancer patients: A consensus-based approach to identify highly discriminating metabolites. Oncotarget 2016 7 5 5815 5829 10.18632/oncotarget.6808 26735340
    [Google Scholar]
  144. Arnold M. Sierra M.S. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017 66 4 683 691 10.1136/gutjnl‑2015‑310912 26818619
    [Google Scholar]
  145. Fung K.Y.C. Tabor B. Buckley M.J. Priebe I.K. Purins L. Pompeia C. Brierley G.V. Lockett T. Gibbs P. Tie J. McMurrick P. Moore J. Ruszkiewicz A. Nice E. Adams T.E. Burgess A. Cosgrove L.J. Blood-based protein biomarker panel for the detection of colorectal cancer. PLoS One 2015 10 3 e0120425 10.1371/journal.pone.0120425 25793510
    [Google Scholar]
  146. Junjun Y. Yao H. Yuanyuan Z. Xiaoning Z. Xiqiao Z. Expression of sphingosine-1-phosphate receptor 2 in human colon cancer and its correlation with cancer migration and invasion. Gastroenterology 2017 152 5 S1024 10.1016/S0016‑5085(17)33467‑4
    [Google Scholar]
  147. Kawamori T. Kaneshiro T. Okumura M. Maalouf S. Uflacker A. Bielawski J. Hannun Y.A. Obeid L.M. Role for sphingosine kinase 1 in colon carcinogenesis. FASEB J. 2009 23 2 405 414 10.1096/fj.08‑117572 18824518
    [Google Scholar]
  148. Samuhasaneeto S. Promagsorn S. Punsawad C. Sphingosine 1-phosphate receptor 4 expression in colorectal cancer patients. Walailak J. Sci. Technol. 2017 14 8 663 669
    [Google Scholar]
  149. Long J. Xie Y. Yin J. Lu W. Fang S. SphK1 promotes tumor cell migration and invasion in colorectal cancer. Tumour Biol. 2016 37 5 6831 6836 10.1007/s13277‑015‑4542‑4 26662312
    [Google Scholar]
  150. Tan S.S.L. Khin L.W. Wong L. Yan B. Ong C.W. Datta A. Salto-Tellez M. Lam Y. Yap C.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. 2014 5 2 e51 10.1038/ctg.2013.21 24572701
    [Google Scholar]
  151. Rosa R. Marciano R. Malapelle U. Formisano L. Nappi L. D’Amato C. D’Amato V. Damiano V. Marfè G. Del Vecchio S. Zannetti A. Greco A. De Stefano A. Carlomagno C. Veneziani B.M. Troncone G. De Placido S. Bianco R. Sphingosine kinase 1 overexpression contributes to cetuximab resistance in human colorectal cancer models. Clin. Cancer Res. 2013 19 1 138 147 10.1158/1078‑0432.CCR‑12‑1050 23166225
    [Google Scholar]
  152. Dai X. Li T. Bai Z. Yang Y. Liu X. Zhan J. Shi B. Breast cancer intrinsic subtype classification, clinical use and future trends. Am. J. Cancer Res. 2015 5 10 2929 2943 26693050
    [Google Scholar]
  153. Nagahashi M. Tsuchida J. Moro K. Hasegawa M. Tatsuda K. Woelfel I.A. Takabe K. Wakai T. High levels of sphingolipids in human breast cancer. J. Surg. Res. 2016 204 2 435 444 10.1016/j.jss.2016.05.022 27565080
    [Google Scholar]
  154. Nagahashi M. Yamada A. Miyazaki H. Allegood J.C. Tsuchida J. Aoyagi T. Huang W.C. Terracina K.P. Adams B.J. Rashid O.M. Milstien S. Wakai T. Spiegel S. Takabe K. 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. Neoplasia 2016 21 1-2 9 17 10.1007/s10911‑016‑9354‑7 27194029
    [Google Scholar]
  155. Desai S.A. Patel V.P. Bhosle K.P. Nagare S.D. Thombare K.C. The tumor microenvironment: Shaping cancer progression and treatment response. J. Chemother. 2025 37 1 15 44 10.1080/1120009X.2023.2300224 38179655
    [Google Scholar]
  156. Tsuchida J. Nagahashi M. Nakajima M. Moro K. Tatsuda K. Ramanathan R. Takabe K. Wakai T. Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis. J. Surg. Res. 2016 205 1 85 94 10.1016/j.jss.2016.06.022 27621003
    [Google Scholar]
  157. Nagahashi M. Ramachandran S. Kim E.Y. Allegood J.C. Rashid O.M. Yamada A. Zhao R. Milstien S. Zhou H. Spiegel S. Takabe K. Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis. Cancer Res. 2012 72 3 726 735 10.1158/0008‑5472.CAN‑11‑2167 22298596
    [Google Scholar]
/content/journals/dmbl/10.2174/0118723128377799250214075521
Loading
/content/journals/dmbl/10.2174/0118723128377799250214075521
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: lipid ; signaling pathway ; biomarker ; novel treatment ; melanoma cells ; sphingolipid ; Cancer
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