Abstract
Metabolic reprogramming and altered cellular energetics have been recently established as an important cancer hallmark. The modulation of glucose metabolism is one of the important characteristic features of metabolic reprogramming in cancer. It contributes to oncogenic progression by supporting the increased biosynthetic and bio-energetic demands of tumor cells. This oncogenic transformation consequently results in elevated expression of glucose transporters in these cells. Moreover, various cancers exhibit abnormal transporter expression patterns compared to normal tissues. Recent investigations have underlined the significance of glucose transporters in regulating cancer cell survival, proliferation, and metastasis. Abnormal regulation of these transporters, which exhibit varying affinities for hexoses, could enable cancer cells to efficiently manage their energy supply, offering a crucial edge for proliferation. Exploiting the upregulated expression of glucose transporters, GLUTs, and Sodium Linked Glucose Transporters (SGLTs), could serve as a novel therapeutic intervention for anti-cancer drug discovery as well as provide a unique targeting approach for drug delivery to specific tumor tissues. This review aims to discussthe previous and emerging research on the expression of various types of glucose transporters in tumor tissues, the role of glucose transport inhibitors as a cancer therapy intervention as well as emerging GLUT/SGLT-mediated drug delivery strategies that can be therapeutically employed to target various cancers.
Keywords: Cancer, glucose metabolism, glucose transporters, glycoconjugation, metabolic reprogramming, nanoparticle, drug-delivery.
[http://dx.doi.org/10.1126/science.aaw5473] [PMID: 32273439]
[http://dx.doi.org/10.1038/nrc2981] [PMID: 21258394]
[http://dx.doi.org/10.1016/j.ccr.2008.05.005] [PMID: 18538731]
[http://dx.doi.org/10.1038/nature11706] [PMID: 23151579]
[http://dx.doi.org/10.1111/cas.12085] [PMID: 23279446]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[http://dx.doi.org/10.1038/s41422-022-00614-0] [PMID: 35105939]
[http://dx.doi.org/10.1038/s41467-022-32101-w] [PMID: 35931676]
[http://dx.doi.org/10.1016/B978-0-12-823397-9.00006-5]
[http://dx.doi.org/10.3390/ijms23031155] [PMID: 35163079]
[http://dx.doi.org/10.3390/cells10051056] [PMID: 33946927]
[http://dx.doi.org/10.1038/s41392-023-01332-8] [PMID: 36797231]
[http://dx.doi.org/10.1186/s40170-020-00237-2] [PMID: 33413672]
[http://dx.doi.org/10.3389/fonc.2020.00317] [PMID: 32211335]
[http://dx.doi.org/10.1126/science.1174229] [PMID: 19661383]
[http://dx.doi.org/10.3389/fcell.2020.603837] [PMID: 33511116]
[http://dx.doi.org/10.1126/sciadv.1600200] [PMID: 27386546]
[http://dx.doi.org/10.1155/2010/205357] [PMID: 20706540]
[http://dx.doi.org/10.1016/j.lfs.2020.118603] [PMID: 33091446]
[http://dx.doi.org/10.1126/science.1160809] [PMID: 19460998]
[http://dx.doi.org/10.4103/1477-3163.119606] [PMID: 24227994]
[http://dx.doi.org/10.3389/fonc.2022.820173] [PMID: 35178349]
[http://dx.doi.org/10.1016/j.molmet.2019.11.011] [PMID: 31926876]
[http://dx.doi.org/10.1016/j.molcel.2021.08.026] [PMID: 34547236]
[http://dx.doi.org/10.1038/s41580-019-0123-5] [PMID: 30976106]
[http://dx.doi.org/10.1085/jgp.8.6.519] [PMID: 19872213]
[PMID: 7391842]
[http://dx.doi.org/10.1097/CCO.0b013e328356da72] [PMID: 22913968]
[http://dx.doi.org/10.1152/ajpendo.00712.2009] [PMID: 20009031]
[http://dx.doi.org/10.1080/09687680110090456] [PMID: 11780753]
[http://dx.doi.org/10.1007/s00424-003-1085-0] [PMID: 12750891]
[http://dx.doi.org/10.1002/iub.315] [PMID: 20209635]
[http://dx.doi.org/10.3390/cancers13164184] [PMID: 34439338]
[http://dx.doi.org/10.1016/j.metabol.2015.10.007] [PMID: 26773935]
[http://dx.doi.org/10.4067/S0716-97602002000100004] [PMID: 12125211]
[http://dx.doi.org/10.1002/jcp.20166] [PMID: 15389572]
[http://dx.doi.org/10.1038/nrc3038] [PMID: 21508971]
[http://dx.doi.org/10.1007/s12253-012-9500-5] [PMID: 22270867]
[http://dx.doi.org/10.1016/S0014-5793(02)03058-2] [PMID: 12135767]
[http://dx.doi.org/10.4103/jomfp.JOMFP_22_18] [PMID: 31942129]
[http://dx.doi.org/10.2174/138920207780368187] [PMID: 18660845]
[http://dx.doi.org/10.1016/S0006-291X(05)81022-8] [PMID: 2256938]
[http://dx.doi.org/10.1177/147323001003800601] [PMID: 21226991]
[http://dx.doi.org/10.1002/jcp.20606] [PMID: 16523487]
[http://dx.doi.org/10.18632/oncotarget.15171] [PMID: 28187435]
[http://dx.doi.org/10.1016/j.gene.2018.12.006] [PMID: 30552981]
[http://dx.doi.org/10.7150/jca.30772] [PMID: 31598171]
[http://dx.doi.org/10.5301/JBM.2011.8550] [PMID: 21786248]
[http://dx.doi.org/10.1007/s10120-015-0577-x] [PMID: 26643879]
[http://dx.doi.org/10.1016/S0190-9622(97)70174-9] [PMID: 9344196]
[http://dx.doi.org/10.1016/S0021-9258(19)39181-1] [PMID: 2182619]
[http://dx.doi.org/10.1042/bj2900701] [PMID: 8457197]
[http://dx.doi.org/10.1073/pnas.85.15.5434] [PMID: 3399500]
[http://dx.doi.org/10.1152/ajpcell.1990.259.2.C279] [PMID: 1701966]
[http://dx.doi.org/10.2337/diabetes.49.9.1485] [PMID: 10969832]
[http://dx.doi.org/10.1007/s00125-014-3451-1] [PMID: 25421524]
[http://dx.doi.org/10.1096/fj.201800360R] [PMID: 29913554]
[http://dx.doi.org/10.3892/mmr_00000300] [PMID: 21472282]
[http://dx.doi.org/10.1007/BF02738882] [PMID: 12114701]
[http://dx.doi.org/10.18632/oncotarget.20266] [PMID: 28978124]
[http://dx.doi.org/10.3748/wjg.v22.i45.9933] [PMID: 28018100]
[PMID: 8364915]
[http://dx.doi.org/10.1021/bc060184s] [PMID: 17444608]
[http://dx.doi.org/10.1002/1097-0142(19931115)72:10<2979::AID-CNCR2820721020>3.0.CO;2-X] [PMID: 8221565]
[http://dx.doi.org/10.1158/0008-5472.CAN-09-4615] [PMID: 20647326]
[PMID: 8421107]
[http://dx.doi.org/10.2337/diab.43.12.1413] [PMID: 7958492]
[PMID: 10522065]
[http://dx.doi.org/10.1210/endo.132.6.8504756] [PMID: 8504756]
[http://dx.doi.org/10.1111/j.1365-2362.2007.01786.x] [PMID: 17373964]
[http://dx.doi.org/10.1016/0169-328X(94)90183-X] [PMID: 7877454]
[http://dx.doi.org/10.1002/(SICI)1097-0142(19970915)80:6<1046::AID-CNCR6>3.0.CO;2-7] [PMID: 9305704]
[http://dx.doi.org/10.1016/j.lungcan.2010.08.017] [PMID: 20884076]
[http://dx.doi.org/10.1111/j.1464-410X.2007.06765.x] [PMID: 17437443]
[http://dx.doi.org/10.1016/j.lungcan.2006.08.018] [PMID: 17046099]
[PMID: 9252709]
[http://dx.doi.org/10.1002/jcp.30189] [PMID: 33421130]
[http://dx.doi.org/10.3390/cells8121568] [PMID: 31817208]
[http://dx.doi.org/10.1038/s41392-020-00220-9] [PMID: 32873793]
[http://dx.doi.org/10.1007/s00432-015-1992-4] [PMID: 26048031]
[http://dx.doi.org/10.1007/s13277-014-2838-4] [PMID: 25412955]
[http://dx.doi.org/10.1016/j.yexcr.2015.04.007] [PMID: 25907297]
[http://dx.doi.org/10.1002/(SICI)1097-0215(19990118)80:2<194::AID-IJC6>3.0.CO;2-M] [PMID: 9935199]
[http://dx.doi.org/10.1186/s12964-020-00586-x] [PMID: 32493394]
[http://dx.doi.org/10.3390/molecules15042374] [PMID: 20428049]
[http://dx.doi.org/10.1016/S0005-2736(96)00217-9] [PMID: 9059504]
[http://dx.doi.org/10.1074/jbc.M000988200] [PMID: 10862609]
[http://dx.doi.org/10.1089/thy.2004.14.806] [PMID: 15588375]
[PMID: 9293783]
[http://dx.doi.org/10.1182/blood-2011-09-377846] [PMID: 22452979]
[http://dx.doi.org/10.1016/S0021-9258(18)42067-4] [PMID: 1634504]
[PMID: 8333543]
[http://dx.doi.org/10.1038/s41598-019-45803-x] [PMID: 31243309]
[http://dx.doi.org/10.1210/endo.132.1.8419132] [PMID: 8419132]
[http://dx.doi.org/10.1186/1741-7007-12-8] [PMID: 24484968]
[http://dx.doi.org/10.1186/s40170-020-00222-9] [PMID: 32670573]
[http://dx.doi.org/10.1038/s41420-018-0038-5] [PMID: 29531835]
[http://dx.doi.org/10.1002/jcb.23379] [PMID: 21938742]
[http://dx.doi.org/10.1007/s43440-021-00281-9] [PMID: 34052986]
[http://dx.doi.org/10.2147/OTT.S205522] [PMID: 31371983]
[http://dx.doi.org/10.1073/pnas.93.5.1847] [PMID: 8700847]
[http://dx.doi.org/10.1007/s10565-019-09478-4] [PMID: 31102011]
[http://dx.doi.org/10.3892/or.2010.1096] [PMID: 21165569]
[http://dx.doi.org/10.1371/journal.pone.0026902] [PMID: 22073218]
[http://dx.doi.org/10.1152/ajpgi.00396.2003] [PMID: 15033637]
[http://dx.doi.org/10.1152/ajpendo.00296.2009] [PMID: 19797240]
[http://dx.doi.org/10.1074/jbc.M312226200] [PMID: 14739288]
[http://dx.doi.org/10.1038/onc.2014.119] [PMID: 24858040]
[http://dx.doi.org/10.4081/oncol.2022.561] [PMID: 35340885]
[http://dx.doi.org/10.1016/S1096-7192(02)00018-5] [PMID: 12175779]
[http://dx.doi.org/10.1080/09687860500166143] [PMID: 16154905]
[http://dx.doi.org/10.1006/bbrc.2001.6101] [PMID: 11741323]
[http://dx.doi.org/10.1042/bj3500771] [PMID: 10970791]
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0254] [PMID: 25205105]
[http://dx.doi.org/10.1016/j.cellsig.2020.109688] [PMID: 32512041]
[http://dx.doi.org/10.1074/jbc.275.7.4607] [PMID: 10671487]
[http://dx.doi.org/10.1111/j.1469-7580.2010.01291.x] [PMID: 20819112]
[http://dx.doi.org/10.1016/S0006-291X(03)01417-7] [PMID: 12914765]
[http://dx.doi.org/10.1152/ajpendo.2002.282.3.E733] [PMID: 11832379]
[http://dx.doi.org/10.1016/S0304-3835(03)00010-7] [PMID: 12706881]
[PMID: 29187448]
[http://dx.doi.org/10.1016/j.canlet.2020.09.012] [PMID: 32946964]
[http://dx.doi.org/10.1002/cncr.11293] [PMID: 12673735]
[http://dx.doi.org/10.1530/ERC-17-0051] [PMID: 29431615]
[http://dx.doi.org/10.7150/jca.10429] [PMID: 25561978]
[http://dx.doi.org/10.1006/mgme.2001.3212] [PMID: 11592815]
[http://dx.doi.org/10.1006/geno.2000.6457] [PMID: 11247674]
[http://dx.doi.org/10.1093/emboj/20.16.4467] [PMID: 11500374]
[http://dx.doi.org/10.1111/jdi.13255] [PMID: 32196987]
[http://dx.doi.org/10.1007/s12551-015-0186-2] [PMID: 28510148]
[http://dx.doi.org/10.1007/s00424-003-1202-0] [PMID: 12748858]
[http://dx.doi.org/10.1152/physrev.00055.2009] [PMID: 21527736]
[http://dx.doi.org/10.2133/dmpk.20.452] [PMID: 16415531]
[http://dx.doi.org/10.1038/ng0296-216] [PMID: 8563765]
[http://dx.doi.org/10.1016/S0925-4439(98)00109-4] [PMID: 10036327]
[http://dx.doi.org/10.1111/j.1349-7006.2001.tb01175.x] [PMID: 11509120]
[http://dx.doi.org/10.1080/07357900801956363] [PMID: 18853313]
[http://dx.doi.org/10.1016/S1368-8375(03)00129-5] [PMID: 14662412]
[http://dx.doi.org/10.1007/s10266-011-0033-2] [PMID: 21607591]
[http://dx.doi.org/10.1007/s12032-010-9696-8] [PMID: 21080109]
[http://dx.doi.org/10.1007/s00404-011-2166-5] [PMID: 22159627]
[http://dx.doi.org/10.1002/1878-0261.12530] [PMID: 31199048]
[http://dx.doi.org/10.1016/j.ccr.2008.03.015] [PMID: 18455122]
[http://dx.doi.org/10.1186/s12885-021-09060-4] [PMID: 35090421]
[http://dx.doi.org/10.1038/s41598-017-11674-3] [PMID: 28974690]
[http://dx.doi.org/10.4172/1948-5956.1000159]
[http://dx.doi.org/10.1016/j.cellsig.2021.110192] [PMID: 34774990]
[http://dx.doi.org/10.1073/pnas.1511698112] [PMID: 26170283]
[http://dx.doi.org/10.1002/ijc.31193] [PMID: 29205334]
[http://dx.doi.org/10.12659/MSM.902530] [PMID: 28763435]
[http://dx.doi.org/10.1507/endocrj.EJ19-0428] [PMID: 31776304]
[http://dx.doi.org/10.1007/s10571-022-01221-8] [PMID: 35435536]
[http://dx.doi.org/10.1073/pnas.1733027100] [PMID: 13130073]
[http://dx.doi.org/10.1016/j.mam.2012.11.002] [PMID: 23506865]
[http://dx.doi.org/10.1007/s13300-010-0006-4] [PMID: 22127746]
[http://dx.doi.org/10.1016/j.ejphar.2012.06.033] [PMID: 22766068]
[http://dx.doi.org/10.1016/j.lfs.2004.10.016] [PMID: 15607332]
[http://dx.doi.org/10.1016/j.ymben.2019.09.006] [PMID: 31526853]
[http://dx.doi.org/10.1186/1471-2164-14-55] [PMID: 23350875]
[http://dx.doi.org/10.1097/MED.0b013e328357f0cb] [PMID: 22922366]
[http://dx.doi.org/10.1016/j.febslet.2011.12.027] [PMID: 22212718]
[http://dx.doi.org/10.1371/journal.pone.0056681] [PMID: 23451068]
[http://dx.doi.org/10.1080/21623945.2018.1516098] [PMID: 30161013]
[http://dx.doi.org/10.1016/0888-7543(95)80052-N] [PMID: 7789985]
[http://dx.doi.org/10.1002/jbmr.240] [PMID: 20818642]
[PMID: 31768373]
[http://dx.doi.org/10.1038/s41419-022-05017-y] [PMID: 35760803]
[http://dx.doi.org/10.1146/annurev-physiol-022516-034125] [PMID: 28192058]
[http://dx.doi.org/10.1210/jcem.83.5.4839] [PMID: 9589686]
[http://dx.doi.org/10.1210/jc.2002-021544] [PMID: 12679487]
[http://dx.doi.org/10.1016/j.bmcl.2010.02.027] [PMID: 20194024]
[http://dx.doi.org/10.3389/fphar.2022.1035510] [PMID: 36386187]
[http://dx.doi.org/10.1210/en.2014-1260] [PMID: 24932809]
[http://dx.doi.org/10.3390/ijms17091443] [PMID: 27589739]
[http://dx.doi.org/10.1097/MPA.0b013e3181735ccb] [PMID: 18953257]
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0569] [PMID: 19001437]
[http://dx.doi.org/10.1002/jcb.22984] [PMID: 21328458]
[http://dx.doi.org/10.1080/01635581.2015.1002625] [PMID: 25719685]
[http://dx.doi.org/10.3390/cancers13020188] [PMID: 33430318]
[http://dx.doi.org/10.1016/j.biochi.2016.03.014] [PMID: 27039889]
[http://dx.doi.org/10.1016/j.yexcr.2013.05.001] [PMID: 23664836]
[http://dx.doi.org/10.1271/bbb.63.719] [PMID: 10361685]
[http://dx.doi.org/10.1089/jmf.2007.116] [PMID: 18158826]
[http://dx.doi.org/10.1038/srep43864] [PMID: 28262837]
[http://dx.doi.org/10.1210/me.2008-0179] [PMID: 19106193]
[http://dx.doi.org/10.1074/jbc.M114.628826] [PMID: 25847249]
[http://dx.doi.org/10.1186/2049-3002-1-14] [PMID: 24280290]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1088] [PMID: 25542900]
[http://dx.doi.org/10.1126/scitranslmed.3002394] [PMID: 21813754]
[http://dx.doi.org/10.1016/j.canlet.2010.07.002] [PMID: 20678861]
[http://dx.doi.org/10.1371/journal.pone.0023205] [PMID: 21826239]
[http://dx.doi.org/10.1016/j.canlet.2007.07.021] [PMID: 17910902]
[http://dx.doi.org/10.1002/jcb.20270] [PMID: 15449313]
[http://dx.doi.org/10.1016/S1499-3872(11)60010-6] [PMID: 21269938]
[http://dx.doi.org/10.1016/j.febslet.2012.01.006] [PMID: 22265971]
[http://dx.doi.org/10.1038/oncsis.2012.21] [PMID: 23552737]
[PMID: 12067998]
[http://dx.doi.org/10.1016/j.molmed.2006.07.007] [PMID: 16899408]
[http://dx.doi.org/10.1007/s00424-020-02448-4] [PMID: 32820343]
[http://dx.doi.org/10.3390/biomedicines11071867] [PMID: 37509506]
[http://dx.doi.org/10.1097/MED.0000000000000311] [PMID: 27898586]
[http://dx.doi.org/10.3389/fmed.2021.777861] [PMID: 34988095]
[http://dx.doi.org/10.1038/s42003-023-05289-w] [PMID: 37684337]
[http://dx.doi.org/10.1016/j.neo.2021.02.003] [PMID: 33784591]
[http://dx.doi.org/10.5306/wjco.v11.i3.110] [PMID: 32257842]
[http://dx.doi.org/10.1039/c3sc22205e] [PMID: 24077675]
[http://dx.doi.org/10.1007/s002800050248] [PMID: 7850916]
[http://dx.doi.org/10.1007/s00280-009-1028-3] [PMID: 19479254]
[http://dx.doi.org/10.1200/JCO.2000.18.20.3535] [PMID: 11032596]
[http://dx.doi.org/10.1016/j.ejca.2008.12.022] [PMID: 19188061]
[http://dx.doi.org/10.1016/S0014-2999(96)00796-0] [PMID: 9016941]
[http://dx.doi.org/10.1016/S0008-6215(96)00328-X] [PMID: 9129293]
[http://dx.doi.org/10.3987/COM-00-S(I)34]
[http://dx.doi.org/10.1248/bpb.31.1155] [PMID: 18520047]
[http://dx.doi.org/10.1021/jm8006257] [PMID: 19053781]
[http://dx.doi.org/10.18632/oncotarget.17073] [PMID: 28467806]
[http://dx.doi.org/10.1158/0008-5472.CAN-12-2072] [PMID: 23396585]
[http://dx.doi.org/10.3390/ijms23031685] [PMID: 35163607]
[http://dx.doi.org/10.1186/s12943-023-01865-0] [PMID: 37814270]
[http://dx.doi.org/10.1016/j.biomaterials.2013.09.094] [PMID: 24125772]
[http://dx.doi.org/10.1002/jps.23928] [PMID: 24619482]
[http://dx.doi.org/10.1016/j.ccr.2012.02.022] [PMID: 22439926]
[http://dx.doi.org/10.1016/j.tcb.2017.06.003] [PMID: 28734735]
[http://dx.doi.org/10.3389/fonc.2019.01143] [PMID: 31737570]
[http://dx.doi.org/10.1111/febs.13402] [PMID: 26255648]
[http://dx.doi.org/10.3389/fphar.2023.1113378] [PMID: 37007004]
[http://dx.doi.org/10.1038/s41417-021-00318-4] [PMID: 33712707]
[http://dx.doi.org/10.3390/cells10020304] [PMID: 33540679]
[http://dx.doi.org/10.1371/journal.pone.0234613] [PMID: 32555715]
[http://dx.doi.org/10.1016/j.canlet.2015.10.027] [PMID: 26546872]
[http://dx.doi.org/10.1158/0008-5472.CAN-12-1949] [PMID: 22850421]
[http://dx.doi.org/10.1073/pnas.94.13.6658] [PMID: 9192621]
[http://dx.doi.org/10.1007/s10555-014-9506-4] [PMID: 24984804]
[http://dx.doi.org/10.4161/cc.10.11.15659] [PMID: 21558814]
[http://dx.doi.org/10.1016/j.yexcr.2017.01.013] [PMID: 28132882]
[http://dx.doi.org/10.1038/s41467-024-46504-4] [PMID: 38509063]
[http://dx.doi.org/10.21037/atm-20-1114] [PMID: 32953828]
[http://dx.doi.org/10.1016/j.cmet.2019.06.001] [PMID: 31269428]
[http://dx.doi.org/10.1615/CritRevImmunol.v32.i6.10] [PMID: 23428224]
[http://dx.doi.org/10.3389/fimmu.2023.1166487] [PMID: 37138860]
[http://dx.doi.org/10.1002/1873-3468.12771] [PMID: 28771701]
[http://dx.doi.org/10.1016/j.canlet.2017.10.037] [PMID: 29111350]
[http://dx.doi.org/10.1080/2162402X.2016.1191731] [PMID: 27622062]
[http://dx.doi.org/10.1021/acs.jproteome.6b00604] [PMID: 27809537]
[http://dx.doi.org/10.3892/ijo.2023.5518] [PMID: 37144503]
[http://dx.doi.org/10.1038/s41420-021-00401-7] [PMID: 33462221]
[PMID: 21155627]
[http://dx.doi.org/10.3389/fonc.2021.697894] [PMID: 34327138]
[http://dx.doi.org/10.3389/fimmu.2017.01300] [PMID: 29081778]
[http://dx.doi.org/10.1038/s41467-017-02733-4] [PMID: 29386513]
[http://dx.doi.org/10.1016/j.bmc.2013.12.041] [PMID: 24398380]
[http://dx.doi.org/10.1016/j.molcel.2020.05.034] [PMID: 32559423]
[http://dx.doi.org/10.1126/scitranslmed.aad7118] [PMID: 26936508]
[http://dx.doi.org/10.1038/s41598-024-52160-x] [PMID: 38243049]