Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.
cancer therapy
drug design and discovery
kinase inhibitors
sphingosine kinase
sphingosine metabolism
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
15 Apr 2021
15 Apr 2021
Historique:
received:
13
02
2021
revised:
11
03
2021
accepted:
03
04
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
1
5
2021
Statut:
epublish
Résumé
Sphingolipid metabolites have emerged as critical players in the regulation of various physiological processes. Ceramide and sphingosine induce cell growth arrest and apoptosis, whereas sphingosine-1-phosphate (S1P) promotes cell proliferation and survival. Here, we present an overview of sphingolipid metabolism and the compartmentalization of various sphingolipid metabolites. In addition, the sphingolipid rheostat, a fine metabolic balance between ceramide and S1P, is discussed. Sphingosine kinase (SphK) catalyzes the synthesis of S1P from sphingosine and modulates several cellular processes and is found to be essentially involved in various pathophysiological conditions. The regulation and biological functions of SphK isoforms are discussed. The functions of S1P, along with its receptors, are further highlighted. The up-regulation of SphK is observed in various cancer types and is also linked to radio- and chemoresistance and poor prognosis in cancer patients. Implications of the SphK/S1P signaling axis in human pathologies and its inhibition are discussed in detail. Overall, this review highlights current findings on the SphK/S1P signaling axis from multiple angles, including their functional role, mechanism of activation, involvement in various human malignancies, and inhibitor molecules that may be used in cancer therapy.
Identifiants
pubmed: 33920887
pii: cancers13081898
doi: 10.3390/cancers13081898
pmc: PMC8071327
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : Indian Council of Medical Research
ID : ISRM/12(22)/2020
Références
Leukemia. 2016 Nov;30(11):2142-2151
pubmed: 27461062
J Nat Prod. 2002 Oct;65(10):1505-6
pubmed: 12398554
Mol Cancer Ther. 2005 Sep;4(9):1430-8
pubmed: 16170036
Nature. 2014 Jun 5;510(7503):58-67
pubmed: 24899305
Gene. 2000 Jun 13;251(1):19-26
pubmed: 10863092
BMC Cancer. 2014 Oct 25;14:783
pubmed: 25344679
Nature. 1996 Jun 27;381(6585):800-3
pubmed: 8657285
Clin Exp Pharmacol Physiol. 2019 Sep;46(9):861-871
pubmed: 31206801
J Urol. 2003 Jun;169(6):2372-7
pubmed: 12771800
J Biol Chem. 2009 Feb 6;284(6):3408-17
pubmed: 19074142
Sci Rep. 2017 Dec 5;7(1):16978
pubmed: 29208982
Sci Signal. 2015 Jun 16;8(381):ra58
pubmed: 26082434
Biochim Biophys Acta. 2008 Jan-Feb;1781(1-2):40-51
pubmed: 18068681
Biochem Cell Biol. 2018 Dec;96(6):742-751
pubmed: 29940125
Cancer Med. 2019 Apr;8(4):1731-1743
pubmed: 30791228
Anticancer Agents Med Chem. 2012 May;12(4):340-63
pubmed: 21707511
Cell Signal. 2008 Jun;20(6):1010-8
pubmed: 18191382
J Biol Chem. 2010 Jan 1;285(1):483-92
pubmed: 19854831
Chem Commun (Camb). 2013 Mar 14;49(21):2136-8
pubmed: 23388656
Cell. 2012 Mar 2;148(5):988-1000
pubmed: 22385963
Adv Cancer Res. 2013;117:37-58
pubmed: 23290776
Lancet. 2018 Mar 31;391(10127):1263-1273
pubmed: 29576505
J Biol Chem. 2005 Nov 4;280(44):37118-29
pubmed: 16118219
Biochemistry. 2001 Nov 20;40(46):14053-60
pubmed: 11705398
Clin Neuropharmacol. 2010 Mar-Apr;33(2):91-101
pubmed: 20061941
J Biol Chem. 2000 Jun 30;275(26):19513-20
pubmed: 10751414
Cancer Transl Med. 2017 Jul-Aug;3(4):109-121
pubmed: 28890935
Indian J Cancer. 2014 Oct-Dec;51(4):524-9
pubmed: 26842184
Autophagy. 2010 Nov;6(8):1157-67
pubmed: 20935520
Cancer Res. 2002 Mar 1;62(5):1410-9
pubmed: 11888913
Cancer Cell. 2006 Mar;9(3):225-38
pubmed: 16530706
J Gastrointest Cancer. 2020 Jun;51(2):716-717
pubmed: 31093935
J Transl Med. 2017 Mar 15;15(1):58
pubmed: 28298211
Trends Endocrinol Metab. 2007 Oct;18(8):300-7
pubmed: 17904858
Anticancer Agents Med Chem. 2011 Nov;11(9):810-7
pubmed: 21707490
Mol Cancer Ther. 2017 Dec;16(12):2724-2734
pubmed: 28939554
Curr Genomics. 2017 Feb;18(1):3-26
pubmed: 28503087
Cancer Res. 2003 Sep 15;63(18):5962-9
pubmed: 14522923
Invest New Drugs. 2011 Dec;29(6):1132-42
pubmed: 20473784
Front Pharmacol. 2017 Aug 23;8:556
pubmed: 28878674
Biochem Biophys Res Commun. 2015 May 15;460(4):903-8
pubmed: 25824043
Cell Biol Int. 2018 Nov;42(11):1492-1502
pubmed: 29790626
J Pharmacol Exp Ther. 2010 Apr;333(1):129-39
pubmed: 20061445
FEBS Lett. 2010 May 3;584(9):1728-40
pubmed: 20178791
Exp Biol Med (Maywood). 2016 Feb;241(3):265-72
pubmed: 26376826
Pharmacol Rev. 2008 Jun;60(2):181-95
pubmed: 18552276
Int J Cancer. 1996 May 3;66(3):358-66
pubmed: 8621258
Biochimie. 2010 Jun;92(6):716-23
pubmed: 20167244
PLoS One. 2012;7(9):e44543
pubmed: 22970244
Biochem Biophys Res Commun. 2017 Jun 10;487(4):782-788
pubmed: 28433634
Mediators Inflamm. 2016;2016:8606878
pubmed: 26966342
Cell Death Discov. 2018 Jun 28;4:72
pubmed: 30062053
DNA Cell Biol. 2019 Nov;38(11):1338-1345
pubmed: 31464523
Naunyn Schmiedebergs Arch Pharmacol. 2007 Feb;374(5-6):413-28
pubmed: 17242884
Am J Cancer Res. 2017 Jul 01;7(7):1501-1514
pubmed: 28744400
FASEB J. 2008 Aug;22(8):2629-38
pubmed: 18362204
J Dig Dis. 2014 May;15(5):246-59
pubmed: 24868599
Int J Biol Macromol. 2020 Mar 15;147:177-186
pubmed: 31917989
Trends Cell Biol. 2012 Jan;22(1):50-60
pubmed: 22001186
Cancer Res. 2009 Sep 1;69(17):6915-23
pubmed: 19723667
Med Res Rev. 2015 Sep;35(5):937-67
pubmed: 25850821
Front Immunol. 2017 Mar 14;8:296
pubmed: 28352271
Nat Rev Drug Discov. 2013 Sep;12(9):688-702
pubmed: 23954895
Adv Cancer Res. 2013;117:59-89
pubmed: 23290777
EBioMedicine. 2019 Feb;40:210-223
pubmed: 30587459
J Biol Chem. 2004 Dec 24;279(52):53994-4001
pubmed: 15485866
Am J Cancer Res. 2019 Mar 01;9(3):546-561
pubmed: 30949409
FASEB J. 2001 Mar;15(3):719-30
pubmed: 11259390
Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Oct;1862(10 Pt B):1155-1165
pubmed: 28743537
Nat Rev Drug Discov. 2010 Nov;9(11):883-97
pubmed: 21031003
EMBO J. 2003 Oct 15;22(20):5491-500
pubmed: 14532121
RSC Adv. 2019 Oct 22;9(58):33957-33968
pubmed: 35528925
Front Pharmacol. 2019 Jul 12;10:746
pubmed: 31354475
Biochemistry. 1998 Sep 15;37(37):12892-8
pubmed: 9737868
Cell Signal. 2009 Jun;21(6):836-46
pubmed: 19385042
PLoS One. 2015 Nov 18;10(11):e0143384
pubmed: 26580959
Autophagy. 2009 Feb;5(2):184-93
pubmed: 19098447
Mol Cancer Res. 2019 Apr;17(4):870-881
pubmed: 30655321
Bioorg Med Chem. 2009 Jan 1;17(1):235-41
pubmed: 19056278
Nat Rev Endocrinol. 2020 Apr;16(4):224-233
pubmed: 32060415
FEBS J. 2013 Nov;280(21):5317-36
pubmed: 23638983
Carcinogenesis. 2017 Dec 7;38(12):1218-1227
pubmed: 29028945
J Pharmacol Exp Ther. 2015 Mar;352(3):494-508
pubmed: 25563902
Nat Rev Mol Cell Biol. 2008 Feb;9(2):139-50
pubmed: 18216770
Prostaglandins Other Lipid Mediat. 2013 Oct;106:62-71
pubmed: 23770055
Adv Exp Med Biol. 2010;688:1-23
pubmed: 20919643
Sci Signal. 2017 Mar 28;10(472):
pubmed: 28351953
Cell Signal. 2017 Jun;34:66-75
pubmed: 28302566
Lipids Health Dis. 2010 Feb 05;9:15
pubmed: 20137073
J Biol Chem. 2003 Oct 10;278(41):40330-6
pubmed: 12835323
Adv Exp Med Biol. 2016;893:1-19
pubmed: 26667336
Oncol Rep. 2013 Dec;30(6):2571-8
pubmed: 24100923
FEBS Lett. 2004 Nov 19;577(3):333-8
pubmed: 15556605
J Biol Chem. 2011 Aug 12;286(32):27855-62
pubmed: 21693702
Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Nov;1863(11):1413-1422
pubmed: 30591148
Eur J Cancer. 2015 Sep;51(14):1937-45
pubmed: 26238015
Curr Drug Targets. 2008 Aug;9(8):662-73
pubmed: 18691013
Trends Biochem Sci. 2011 Feb;36(2):97-107
pubmed: 20870412
Cancer Cell Int. 2019 Nov 14;19:295
pubmed: 31807117
Cell Physiol Biochem. 2010;26(1):97-104
pubmed: 20502009
Br J Haematol. 2017 Jul;178(1):155-158
pubmed: 27220679
Adv Cancer Res. 2018;140:295-325
pubmed: 30060814
Med Sci Monit. 2018 Apr 01;24:1912-1923
pubmed: 29605826
Int J Mol Sci. 2017 Sep 02;18(9):
pubmed: 28869494
Spectrochim Acta A Mol Biomol Spectrosc. 2020 Jan 15;225:117453
pubmed: 31446356
Oncotarget. 2017 Nov 6;8(62):105525-105535
pubmed: 29285269
Cell Cycle. 2008 Nov 1;7(21):3362-70
pubmed: 18948750
Adv Cancer Res. 2013;117:201-35
pubmed: 23290781
Cell Biochem Funct. 2015 Oct;33(7):463-77
pubmed: 26486270
Adv Biol Regul. 2018 Jan;67:59-65
pubmed: 29055687
J Biol Chem. 2015 Apr 10;290(15):9660-73
pubmed: 25716317
Eur J Med Chem. 2010 Sep;45(9):4149-56
pubmed: 20598402
IUBMB Life. 2018 Nov;70(11):1164-1176
pubmed: 30281914
Biochim Biophys Acta. 2013 Jan;1831(1):157-66
pubmed: 22801037
Exp Cell Res. 2015 May 1;333(2):195-200
pubmed: 25770011
Clin Cancer Res. 2011 Apr 15;17(8):2484-92
pubmed: 21257722
J Biol Chem. 2010 Nov 12;285(46):35957-66
pubmed: 20837468
Oncotarget. 2016 Apr 26;7(17):23106-27
pubmed: 27036015
Bioorg Med Chem Lett. 2013 Aug 15;23(16):4608-16
pubmed: 23845219
Cancer Res. 2005 Aug 15;65(16):7478-84
pubmed: 16103102
Biochim Biophys Acta. 2008 Sep;1781(9):459-66
pubmed: 18485923
Mol Biol Cell. 2007 Oct;18(10):3810-9
pubmed: 17652460
Curr Med Res Opin. 2016 Jun;32(6):1137-41
pubmed: 26950691
Biochem J. 2012 May 15;444(1):e1-2
pubmed: 22533672
Biomed Pharmacother. 2019 Oct;118:109245
pubmed: 31352240
Pharmacol Res. 2003 May;47(5):393-9
pubmed: 12676513
Anticancer Drugs. 2011 Mar;22(3):245-52
pubmed: 21360847
Science. 2009 Sep 4;325(5945):1254-7
pubmed: 19729656
Clin Cancer Res. 2011 Apr 1;17(7):1839-49
pubmed: 21325072
Int J Mol Sci. 2017 Oct 08;18(10):
pubmed: 28991193
Biochem Biophys Res Commun. 2016 Feb 12;470(3):728-734
pubmed: 26775841
Oncotarget. 2017 May 30;8(22):36898-36929
pubmed: 28415564
J Biol Chem. 2002 Mar 8;277(10):7996-8003
pubmed: 11777919
Sci Rep. 2019 Dec 10;9(1):18727
pubmed: 31822735
Biochem J. 2004 Sep 1;382(Pt 2):527-33
pubmed: 15144238
J Cell Physiol. 2019 Jun;234(6):8162-8181
pubmed: 30456838
Am J Pathol. 2018 Sep;188(9):1949-1952
pubmed: 30026028
Oncotarget. 2015 Mar 30;6(9):7065-83
pubmed: 25788259
Sci Rep. 2017 Jul 17;7(1):5600
pubmed: 28717222
J Cell Biochem. 2019 Apr;120(4):5396-5408
pubmed: 30444039
Blood. 2012 Aug 16;120(7):1458-65
pubmed: 22745305
PLoS One. 2013 Jul 05;8(7):e68328
pubmed: 23861887
Drug Discov Today. 2008 Oct;13(19-20):894-901
pubmed: 18691670
Cell Signal. 2017 Apr;32:85-92
pubmed: 28108260
J Biol Chem. 2003 Nov 21;278(47):46832-9
pubmed: 12954646
Int J Mol Sci. 2020 Mar 17;21(6):
pubmed: 32192225
Pharmacol Ther. 2019 Mar;195:85-99
pubmed: 30347210
Mediators Inflamm. 2017;2017:4806541
pubmed: 29269995
Oxid Med Cell Longev. 2018 Mar 28;2018:4397159
pubmed: 29785244
Int J Mol Med. 2018 May;41(5):2450-2460
pubmed: 29484372
Int J Mol Sci. 2019 Nov 30;20(23):
pubmed: 31801289
Structure. 2013 May 7;21(5):798-809
pubmed: 23602659
Oncotarget. 2016 Apr 12;7(15):20080-92
pubmed: 26956050
J Lipids. 2013;2013:178910
pubmed: 23984075
ACS Chem Biol. 2015 Jan 16;10(1):225-33
pubmed: 25384187
Leuk Res. 2002 Mar;26(3):301-10
pubmed: 11792420
Oncotarget. 2016 Sep 13;7(37):60181-60192
pubmed: 27517489
Nat Rev Cancer. 2010 Jul;10(7):489-503
pubmed: 20555359
Nat Commun. 2014 Sep 25;5:4806
pubmed: 25254944
Pharmacol Ther. 2011 Dec;132(3):352-60
pubmed: 21906625
Anticancer Agents Med Chem. 2012 Jan;12(1):49-75
pubmed: 21707502
J Neurosci. 2011 May 4;31(18):6850-7
pubmed: 21543615
Phytother Res. 2012 Dec;26(12):1927-33
pubmed: 22451302
Hepatology. 2011 Jun;53(6):1943-58
pubmed: 21391227
Mol Cancer Res. 2009 Jan;7(1):23-32
pubmed: 19147534
PLoS One. 2017 Aug 14;12(8):e0182390
pubmed: 28806736
Chem Rev. 2009 Jul;109(7):3012-43
pubmed: 19422222
Cardiovasc Res. 2007 Apr 1;74(1):56-63
pubmed: 17320845
J Exp Clin Cancer Res. 2015 Sep 04;34:94
pubmed: 26337959
Biochem J. 2012 May 15;444(1):79-88
pubmed: 22397330
Life Sci. 2020 May 15;249:117542
pubmed: 32169519
J Cell Biochem. 2015 Oct;116(10):2227-38
pubmed: 25808826
J Biol Chem. 1998 May 15;273(20):12576-83
pubmed: 9575218
Mol Metab. 2014 Jan 28;3(3):252-60
pubmed: 24749054
Nature. 2010 Jun 24;465(7301):1084-8
pubmed: 20577214
World J Gastroenterol. 2010 Apr 21;16(15):1859-66
pubmed: 20397263
Am J Pathol. 2009 Oct;175(4):1464-72
pubmed: 19729475
J Biol Chem. 2007 Sep 14;282(37):27493-27502
pubmed: 17635916
Nat Rev Mol Cell Biol. 2018 Mar;19(3):175-191
pubmed: 29165427
Blood. 2018 May 17;131(20):2235-2246
pubmed: 29615404
J Pharmacol Exp Ther. 2010 May;333(2):454-64
pubmed: 20179157
Cancer Res. 2010 Nov 1;70(21):8651-61
pubmed: 20959468
Cancer Res. 2000 Aug 15;60(16):4468-74
pubmed: 10969794
BMC Cancer. 2016 Aug 31;16:701
pubmed: 27581969
Oncotarget. 2017 Aug 24;8(43):74947-74961
pubmed: 29088837
Prog Lipid Res. 2019 Apr;74:130-144
pubmed: 30876862
Clin Cancer Res. 2015 Apr 15;21(8):1925-1934
pubmed: 25589614
J Exp Med. 2005 Jan 3;201(1):49-54
pubmed: 15623571
FASEB J. 2011 Feb;25(2):600-12
pubmed: 20959514
J Lipid Res. 2009 Apr;50 Suppl:S91-6
pubmed: 19017611
Pharmacol Ther. 2016 Dec;168:143-157
pubmed: 27621206
Int J Mol Med. 2014 Jan;33(1):17-24
pubmed: 24173614
Tumour Biol. 2014 Nov;35(11):10707-14
pubmed: 25070489
J Cell Mol Med. 2015 Oct;19(10):2329-40
pubmed: 26171944
Clin Cancer Res. 2005 Dec 1;11(23):8458-66
pubmed: 16322309
Exp Ther Med. 2018 Jun;15(6):5371-5376
pubmed: 29844803
Front Pharmacol. 2017 Aug 25;8:579
pubmed: 28890699
Brain Sci. 2013 Apr 26;3(2):670-703
pubmed: 24961420
J Neuropathol Exp Neurol. 2005 Aug;64(8):695-705
pubmed: 16106218
World J Gastroenterol. 2014 Aug 14;20(30):10279-87
pubmed: 25132744
Traffic. 2015 Feb;16(2):101-22
pubmed: 25382749
Nat Chem Biol. 2009 Jun;5(6):428-34
pubmed: 19430484
Curr Opin Cell Biol. 2004 Aug;16(4):373-8
pubmed: 15261669
Oncol Rep. 2014 Oct;32(4):1369-73
pubmed: 25109605
Cell Death Dis. 2019 Jan 18;10(2):50
pubmed: 30718502
J Biol Chem. 2005 Mar 18;280(11):9833-41
pubmed: 15590668
Oncol Lett. 2019 Aug;18(2):1259-1266
pubmed: 31423186
Biochim Biophys Acta. 2002 May 23;1582(1-3):94-9
pubmed: 12069815
Updates Surg. 2016 Mar;68(1):7-11
pubmed: 27067591
FASEB J. 2013 Aug;27(8):3155-66
pubmed: 23629860
Oncotarget. 2017 Apr 4;8(14):22800-22810
pubmed: 28206952
J Med Chem. 2013 Nov 27;56(22):9310-27
pubmed: 24164513
Drugs. 2020 Jun;80(8):841-848
pubmed: 32385738
Cancer Cell Int. 2013 Jun 03;13(1):55
pubmed: 23724847
Tumour Biol. 2015 Mar;36(3):1503-9
pubmed: 25537088
Oncotarget. 2015 May 10;6(13):11614-26
pubmed: 25843953
Endocr Relat Cancer. 2007 Jun;14(2):325-35
pubmed: 17639048
J Surg Oncol. 2017 Apr;115(5):619-630
pubmed: 28194798
Biochim Biophys Acta. 2006 Dec;1758(12):2016-26
pubmed: 16996023
Biofactors. 2017 Mar;43(2):272-282
pubmed: 27801960
Biochim Biophys Acta Biomembr. 2017 Sep;1859(9 Pt B):1573-1582
pubmed: 28315304
Br J Pharmacol. 2011 Mar;162(6):1225-38
pubmed: 21091645
Cell Signal. 2010 Oct;22(10):1536-42
pubmed: 20570726
Am J Physiol Cell Physiol. 2009 Aug;297(2):C451-8
pubmed: 19474291
Am J Transl Res. 2016 Nov 15;8(11):4548-4563
pubmed: 27904661
J Lipid Res. 2018 Dec;59(12):2297-2307
pubmed: 30315000
Blood. 2008 Jan 1;111(1):275-84
pubmed: 17761520
Cancer Chemother Pharmacol. 2012 Jul;70(1):49-56
pubmed: 22729159
Biochem J. 2011 Dec 15;440(3):345-53
pubmed: 21848514
Cell Signal. 2009 Jan;21(1):14-21
pubmed: 18768158
Cell Death Discov. 2017 Aug 14;3:17047
pubmed: 29109864