Abstract
G protein-coupled receptors (GPCRs) are highly expressed on a variety of tumour tissues while several GPCR exogenous ligands become marketed pharmaceuticals. In recent decades, cancer stem cells (CSCs) become widely investigated drug targets for cancer therapy but the underlying mechanism is still not fully elucidated. There are vigorous participations of GPCRs in CSCs-related signalling and functions, such as biomarkers for CSCs, activation of Wnt, Hedgehog (HH) and other signalling to facilitate CSCs progressions. This relationship can not only uncover a novel molecular mechanism for GPCR-mediated cancer cell functions but also assist our understanding of maintaining and modulating CSCs. Moreover, GPCR antagonists and monoclonal antibodies could be applied to impair CSCs functions and consequently attenuate tumour growth, some of which have been undergoing clinical studies and are anticipated to turn into marketed anticancer drugs. Therefore, this review summarizes and provides sufficient evidences on the regulation of GPCR signalling in the maintenance, differentiation and pluripotency of CSCs, suggesting that targeting GPCRs on the surface of CSCs could be potential therapeutic strategies for cancer therapy.
Keywords: Cancer stem cells (CSCs), G protein-coupled receptors (GPCRs), cell signalling, cancer therapy, Hedgehog (HH), Wnt.
[http://dx.doi.org/10.1038/nm.4409] [PMID: 28985214]
[http://dx.doi.org/10.1038/nrc3597] [PMID: 24060864]
[http://dx.doi.org/10.1016/j.apsb.2013.02.006]
[http://dx.doi.org/10.1016/j.canlet.2013.08.027] [PMID: 23973264]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0895] [PMID: 17908997]
[http://dx.doi.org/10.1038/nm.2304] [PMID: 21386835]
[http://dx.doi.org/10.3389/fphar.2017.00035] [PMID: 28203204]
[http://dx.doi.org/10.1038/onc.2011.479] [PMID: 22002312]
[http://dx.doi.org/10.3109/09553002.2014.906766] [PMID: 24650104]
[http://dx.doi.org/10.1038/nm.2284] [PMID: 21240262]
[http://dx.doi.org/10.1038/nrclinonc.2015.61] [PMID: 25850553]
[http://dx.doi.org/10.1016/j.pharmthera.2010.10.007] [PMID: 21073897]
[http://dx.doi.org/10.1038/nature08144] [PMID: 19458711]
[http://dx.doi.org/10.1038/nchembio.1025] [PMID: 22810761]
[http://dx.doi.org/10.1038/nrd.2017.178] [PMID: 29075003]
[http://dx.doi.org/10.1038/s41580-018-0049-3] [PMID: 30104700]
[http://dx.doi.org/10.1038/nature11896] [PMID: 23407534]
[http://dx.doi.org/10.1038/s41594-017-0011-7] [PMID: 29323277]
[http://dx.doi.org/10.3390/ijms17050707] [PMID: 27187360]
[http://dx.doi.org/10.1038/nature21713] [PMID: 28358093]
[http://dx.doi.org/10.1038/nature06196] [PMID: 17934449]
[http://dx.doi.org/10.1007/s10549-013-2779-4] [PMID: 24281828]
[http://dx.doi.org/10.1038/nrd3320] [PMID: 21193867]
[http://dx.doi.org/10.1038/nrc2069] [PMID: 17251915]
[http://dx.doi.org/10.1016/S0165-6147(00)01634-5]
[http://dx.doi.org/10.1111/bph.12757] [PMID: 24821440]
[http://dx.doi.org/10.1038/sj.onc.1204188] [PMID: 11313901]
[http://dx.doi.org/10.1046/j.1523-1747.2003.12427.x] [PMID: 12925212]
[http://dx.doi.org/10.1038/nchembio.1611] [PMID: 25271346]
[http://dx.doi.org/10.1152/ajpendo.00551.2012] [PMID: 23592482]
[http://dx.doi.org/10.1038/s41580-018-0041-y] [PMID: 30026541]
[http://dx.doi.org/10.1016/S0166-2236(00)01643-X] [PMID: 11006463]
[http://dx.doi.org/10.1038/onc.2010.402] [PMID: 20818416]
[http://dx.doi.org/10.1074/jbc.M410312200] [PMID: 15489220]
[http://dx.doi.org/10.1021/jm400638v] [PMID: 23895492]
[http://dx.doi.org/10.1074/jbc.M008827200] [PMID: 11083874]
[http://dx.doi.org/10.1074/jbc.274.18.12355] [PMID: 10212206]
[http://dx.doi.org/10.1124/mol.118.115014] [PMID: 30894404]
[http://dx.doi.org/10.1038/nrd3615] [PMID: 22212680]
[http://dx.doi.org/10.1016/j.bmcl.2017.07.002] [PMID: 28705643]
[http://dx.doi.org/10.1038/ncb2048] [PMID: 20418870]
[http://dx.doi.org/10.1038/nature01593] [PMID: 12717450]
[http://dx.doi.org/10.1126/science.1186624] [PMID: 20339075]
[http://dx.doi.org/10.1186/s13058-014-0408-8] [PMID: 25056574]
[http://dx.doi.org/10.1038/nrclinonc.2010.196] [PMID: 21151206]
[http://dx.doi.org/10.1016/j.tips.2018.07.001] [PMID: 30049420]
[http://dx.doi.org/10.1126/science.1222879] [PMID: 22653731]
[http://dx.doi.org/10.1038/35083601] [PMID: 11452312]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2316] [PMID: 17634527]
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679]
[http://dx.doi.org/10.1016/S0092-8674(00)81226-X] [PMID: 9674432]
[http://dx.doi.org/10.1038/nrg2042] [PMID: 17230199]
[http://dx.doi.org/10.1126/science.1085259] [PMID: 12791979]
[http://dx.doi.org/10.1128/MCB.02354-05] [PMID: 16880514]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1495] [PMID: 21363911]
[http://dx.doi.org/10.7150/ijbs.23756] [PMID: 29559846]
[http://dx.doi.org/10.1038/nature10337] [PMID: 21727895]
[http://dx.doi.org/10.1002/stem.1484] [PMID: 23897697]
[http://dx.doi.org/10.1073/pnas.1106083108] [PMID: 21693646]
[PMID: 24711713]
[http://dx.doi.org/10.1182/blood-2013-10-532523] [PMID: 25293777]
[http://dx.doi.org/10.1038/nrc796] [PMID: 12044012]
[http://dx.doi.org/10.1038/nature07737] [PMID: 19169242]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0054] [PMID: 16778178]
[http://dx.doi.org/10.1073/pnas.1500762112] [PMID: 25739959]
[http://dx.doi.org/10.1038/382547a0] [PMID: 8700230]
[http://dx.doi.org/10.1038/ncomms3965] [PMID: 24351982]
[http://dx.doi.org/10.1016/j.ddmec.2008.05.009]
[http://dx.doi.org/10.1016/j.tcb.2007.06.007] [PMID: 17845852]
[http://dx.doi.org/10.1074/jbc.M110.178772] [PMID: 21209076]
[http://dx.doi.org/10.1016/j.celrep.2018.01.018] [PMID: 29386106]
[http://dx.doi.org/10.1016/j.semcdb.2014.05.002] [PMID: 24845016]
[http://dx.doi.org/10.1016/j.cell.2012.12.026] [PMID: 23332756]
[http://dx.doi.org/10.1074/jbc.M115.665810] [PMID: 26451044]
[http://dx.doi.org/10.1101/gad.1948710] [PMID: 20844016]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1701] [PMID: 22052462]
[http://dx.doi.org/10.1016/j.canlet.2008.09.030] [PMID: 19022563]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2823] [PMID: 20530696]
[http://dx.doi.org/10.1073/pnas.1206400109] [PMID: 23019585]
[http://dx.doi.org/10.1002/stem.2426] [PMID: 27301070]
[PMID: 22075757]
[PMID: 26175931]
[http://dx.doi.org/10.1155/2016/5874127] [PMID: 27057280]
[http://dx.doi.org/10.7150/ijbs.13688] [PMID: 27019624]
[http://dx.doi.org/10.1074/jbc.M117.786798] [PMID: 28739799]
[http://dx.doi.org/10.1124/jpet.117.245027] [PMID: 29263243]
[http://dx.doi.org/10.5483/BMBRep.2015.48.2.250] [PMID: 25413305]
[http://dx.doi.org/10.1002/pro.2446] [PMID: 24677446]
[http://dx.doi.org/10.1038/nature22081] [PMID: 28355176]
[http://dx.doi.org/10.1038/nature10408] [PMID: 21927002]
[http://dx.doi.org/10.1007/s10571-013-9951-6] [PMID: 23793848]
[http://dx.doi.org/10.1002/stem.2083] [PMID: 26086949]
[http://dx.doi.org/10.4149/neo_2017_110] [PMID: 27881008]
[http://dx.doi.org/10.1038/ng.239] [PMID: 18849992]
[http://dx.doi.org/10.1038/onc.2012.375] [PMID: 22945646]
[http://dx.doi.org/10.1111/j.1750-3639.2012.00618.x] [PMID: 22805276]
[http://dx.doi.org/10.1007/s12032-015-0486-1] [PMID: 25636507]
[http://dx.doi.org/10.1096/fj.201700897R] [PMID: 29269400]
[http://dx.doi.org/10.1038/ng.3957] [PMID: 28945253]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-3302] [PMID: 27197183]
[http://dx.doi.org/10.1007/BF03349262] [PMID: 18997494]
[http://dx.doi.org/10.1073/pnas.1404943111] [PMID: 24782546]
[http://dx.doi.org/10.1634/stemcells.2004-0342] [PMID: 15888687]
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0948] [PMID: 24785258]
[http://dx.doi.org/10.1186/bcr3423] [PMID: 23663564]
[PMID: 24904289]
[http://dx.doi.org/10.1007/s13277-016-5180-1] [PMID: 27460092]
[http://dx.doi.org/10.1007/s11302-011-9252-9] [PMID: 21818572]
[http://dx.doi.org/10.1101/gad.1071503] [PMID: 12842911]
[http://dx.doi.org/10.1002/glia.22718] [PMID: 25042636]
[http://dx.doi.org/10.4049/jimmunol.0803055] [PMID: 19265162]
[http://dx.doi.org/10.1111/j.1749-6632.2012.06559.x] [PMID: 22901257]
[http://dx.doi.org/10.1016/j.jocn.2012.10.008] [PMID: 23693024]
[http://dx.doi.org/10.1038/nature14897] [PMID: 26331542]
[http://dx.doi.org/10.3390/ijms19071886] [PMID: 29954076]
[http://dx.doi.org/10.1073/pnas.1120068109] [PMID: 22753465]
[http://dx.doi.org/10.1111/j.1349-7006.2007.00701.x] [PMID: 18271942]
[http://dx.doi.org/10.1186/s12885-018-4544-x] [PMID: 29884132]
[http://dx.doi.org/10.1111/cas.13636] [PMID: 29952132]
[http://dx.doi.org/10.1073/pnas.96.7.3546] [PMID: 10097073]
[http://dx.doi.org/10.1016/j.pharmthera.2014.08.005] [PMID: 25172549]
[http://dx.doi.org/10.1126/sciadv.1700090] [PMID: 28691093]
[http://dx.doi.org/10.1007/s13277-015-4342-x] [PMID: 26537584]
[http://dx.doi.org/10.1007/s10238-011-0135-8] [PMID: 21519961]
[http://dx.doi.org/10.1002/jcb.26572] [PMID: 29231999]
[http://dx.doi.org/10.1002/mc.22225] [PMID: 25263583]
[http://dx.doi.org/10.1158/1535-7163.MCT-11-1058] [PMID: 22553355]
[http://dx.doi.org/10.3892/ijo.2012.1597] [PMID: 22923052]
[http://dx.doi.org/10.1097/CCO.0000000000000058] [PMID: 24469022]
[http://dx.doi.org/10.1371/journal.pone.0015262] [PMID: 21203400]
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0731] [PMID: 24634412]
[http://dx.doi.org/10.1111/cas.13019] [PMID: 27461445]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1116] [PMID: 25388167]
[http://dx.doi.org/10.1002/ijc.28193] [PMID: 23564295]
[http://dx.doi.org/10.1002/ijc.28043] [PMID: 23341351]
[http://dx.doi.org/10.1126/scitranslmed.aac7433] [PMID: 26582901]
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0114] [PMID: 27207778]
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0694] [PMID: 29695632]
[http://dx.doi.org/10.1038/s41598-017-15704-y] [PMID: 29127379]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-0561] [PMID: 26719531]
[http://dx.doi.org/10.1111/cas.12475] [PMID: 24981602]
[http://dx.doi.org/10.1002/ijc.31523] [PMID: 29658109]
[PMID: 22016821]
[http://dx.doi.org/10.1038/bjc.2012.105] [PMID: 22644306]