Abstract
Breast cancer is a heterogeneous disease and a leading malignancy around the world. It is a vital cause of untimely mortality among women. Drug resistance is the major challenge for effective cancer therapeutics. In contrast, cancer stem cells (CSCs) are one of the reasons for drug resistance, tumor progression, and metastasis. The small population of CSCs present in each tumor has the ability of self-renewal, differentiation, and tumorigenicity. CSCs are often identified and enriched using a variety of cell surface markers (CD44, CD24, CD133, ABCG2, CD49f, LGR5, SSEA-3, CD70) that exert their functions by different regulatory networks, i.e., Notch, Wnt/β-catenin, hedgehog (Hh), and Hippo signaling pathways. Particularly the Hippo signaling pathway is the emerging and very less explored cancer stem cell pathway. Here, in this review, the Hippo signaling molecules are elaborated with respect to their ability of stemness as epigenetic modulators and how these molecules can be targeted for better cancer treatment and to overcome drug resistance.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.3390/cancers10110422] [PMID: 30400599]
[http://dx.doi.org/10.1136/jcp.2011.090456] [PMID: 21680574]
[http://dx.doi.org/10.4081/ejh.2018.2943] [PMID: 30362671]
[http://dx.doi.org/10.3109/03008207.2015.1066780] [PMID: 26291921]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1479] [PMID: 19509181]
[http://dx.doi.org/10.1073/pnas.0530291100] [PMID: 12629218]
[http://dx.doi.org/10.1111/cas.12817] [PMID: 26362755]
[http://dx.doi.org/10.1016/j.ccr.2007.01.013] [PMID: 17349583]
[http://dx.doi.org/10.1186/bcr1855] [PMID: 18241344]
[http://dx.doi.org/10.1038/nature13851] [PMID: 25327250]
[http://dx.doi.org/10.1186/1476-4598-13-213] [PMID: 25216750]
[http://dx.doi.org/10.1073/pnas.1522602113] [PMID: 26677875]
[http://dx.doi.org/10.1007/s12282-018-0880-6] [PMID: 29948958]
[http://dx.doi.org/10.1002/jcp.28271] [PMID: 30741412]
[http://dx.doi.org/10.1038/nrd4253] [PMID: 24981363]
[http://dx.doi.org/10.1136/jclinpath-2012-201169] [PMID: 23112116]
[http://dx.doi.org/10.1186/1479-5876-9-209] [PMID: 22152097]
[http://dx.doi.org/10.1038/onc.2012.31] [PMID: 22330142]
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.11.033] [PMID: 22206977]
[http://dx.doi.org/10.1016/j.stem.2007.08.014] [PMID: 18371393]
[http://dx.doi.org/10.21873/anticanres.11151] [PMID: 27793889]
[http://dx.doi.org/10.1038/s41392-020-0110-5] [PMID: 32296030]
[http://dx.doi.org/10.3389/fmed.2015.00059] [PMID: 26389119]
[PMID: 28757469]
[http://dx.doi.org/10.3390/cells8050398] [PMID: 31052239]
[http://dx.doi.org/10.3389/fphys.2017.00942] [PMID: 29225579]
[http://dx.doi.org/10.1093/jb/mvt060] [PMID: 23843471]
[http://dx.doi.org/10.1016/j.cell.2015.10.044] [PMID: 26544935]
[http://dx.doi.org/10.4161/cc.22322] [PMID: 23075495]
[http://dx.doi.org/10.1016/j.cell.2012.06.037] [PMID: 22863277]
[http://dx.doi.org/10.1186/1478-811X-11-31] [PMID: 23618389]
[http://dx.doi.org/10.1158/1541-7786.MCR-17-0681] [PMID: 29903770]
[http://dx.doi.org/10.1038/cr.2015.88] [PMID: 26206313]
[http://dx.doi.org/10.1593/neo.08642] [PMID: 18953429]
[http://dx.doi.org/10.3390/cells8050426] [PMID: 31072060]
[http://dx.doi.org/10.1021/acs.biochem.6b00763] [PMID: 27618557]
[http://dx.doi.org/10.1038/nrgastro.2016.59] [PMID: 27147489]
[http://dx.doi.org/10.1038/nature20829] [PMID: 28068668]
[http://dx.doi.org/10.3390/cells9010151] [PMID: 31936297]
[http://dx.doi.org/10.1152/physrev.00005.2014] [PMID: 25287865]
[http://dx.doi.org/10.3390/cancers10030081] [PMID: 29558384]
[http://dx.doi.org/10.1038/ncb1339] [PMID: 16341207]
[http://dx.doi.org/10.1038/emboj.2011.157] [PMID: 21556047]
[http://dx.doi.org/10.1016/j.biopha.2022.113144] [PMID: 35623167]
[http://dx.doi.org/10.1074/jbc.M113.529115] [PMID: 24648515]
[http://dx.doi.org/10.1002/stem.1030] [PMID: 22232070]
[http://dx.doi.org/10.1172/JCI88486] [PMID: 27869648]
[http://dx.doi.org/10.1101/gad.1824509] [PMID: 19952108]
[http://dx.doi.org/10.1111/jcmm.15241] [PMID: 32281270]
[http://dx.doi.org/10.3390/ijms21093236] [PMID: 32375238]
[http://dx.doi.org/10.1074/jbc.M117.780502] [PMID: 28739802]
[http://dx.doi.org/10.1002/hep.30668] [PMID: 31004519]
[http://dx.doi.org/10.1016/j.molcel.2016.05.012] [PMID: 27292796]
[http://dx.doi.org/10.1016/j.bbrc.2017.03.158] [PMID: 28366633]
[http://dx.doi.org/10.3389/fonc.2021.772134] [PMID: 34858852]
[http://dx.doi.org/10.5483/BMBRep.2016.49.7.104] [PMID: 27345717]
[http://dx.doi.org/10.1371/journal.pone.0183178] [PMID: 28820907]
[http://dx.doi.org/10.1158/1541-7786.MCR-17-0004] [PMID: 28923841]
[http://dx.doi.org/10.1038/oncsis.2016.67] [PMID: 27841855]
[http://dx.doi.org/10.1016/j.celrep.2014.09.036] [PMID: 25373897]
[http://dx.doi.org/10.1007/s00018-020-03579-8] [PMID: 32748155]
[PMID: 21193018]
[http://dx.doi.org/10.1016/j.cell.2014.06.013] [PMID: 24976009]
[http://dx.doi.org/10.1038/ncomms9357] [PMID: 26437443]
[http://dx.doi.org/10.1080/23723556.2017.1295127] [PMID: 28616573]
[http://dx.doi.org/10.1684/ejd.2014.2320] [PMID: 24721784]
[PMID: 28757476]
[http://dx.doi.org/10.4161/15384101.2014.967106] [PMID: 25602524]
[http://dx.doi.org/10.1073/pnas.0605579103] [PMID: 16894141]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2696] [PMID: 18413727]
[http://dx.doi.org/10.1016/j.cell.2011.09.048] [PMID: 22078877]
[http://dx.doi.org/10.1016/j.abb.2020.108349] [PMID: 32209309]
[http://dx.doi.org/10.1016/j.burns.2008.12.016] [PMID: 19477596]
[http://dx.doi.org/10.1186/2045-3701-3-31] [PMID: 23985272]
[http://dx.doi.org/10.15252/msb.20145504] [PMID: 25609649]
[http://dx.doi.org/10.3390/cells8060600] [PMID: 31212916]
[http://dx.doi.org/10.1111/cas.12709] [PMID: 26268894]
[http://dx.doi.org/10.1002/path.1024] [PMID: 11748635]
[http://dx.doi.org/10.3389/fgene.2019.00079] [PMID: 30881375]
[http://dx.doi.org/10.1002/ijc.29033] [PMID: 24947242]
[http://dx.doi.org/10.1016/j.yexmp.2012.10.004] [PMID: 23064049]
[http://dx.doi.org/10.1186/s12943-017-0596-9] [PMID: 28148257]
[http://dx.doi.org/10.1042/BSR20171072] [PMID: 28931725]
[http://dx.doi.org/10.1021/cr500350x] [PMID: 25424540]
[http://dx.doi.org/10.7554/eLife.02564] [PMID: 25027438]
[http://dx.doi.org/10.1016/j.celrep.2014.06.017] [PMID: 25017066]
[http://dx.doi.org/10.1074/jbc.M111.334714] [PMID: 22544757]
[http://dx.doi.org/10.1016/j.ccr.2009.09.026] [PMID: 19878874]
[http://dx.doi.org/10.1093/jb/mvr063] [PMID: 21586534]
[http://dx.doi.org/10.1016/j.ydbio.2004.02.019] [PMID: 15183728]
[http://dx.doi.org/10.1016/S1534-5807(03)00227-2] [PMID: 12919684]
[http://dx.doi.org/10.1113/EP088704] [PMID: 32592428]
[http://dx.doi.org/10.1016/j.reth.2021.01.004] [PMID: 33598508]
[http://dx.doi.org/10.1016/j.cell.2007.10.054] [PMID: 18083101]
[http://dx.doi.org/10.1186/s12935-019-0818-x] [PMID: 31049030]
[http://dx.doi.org/10.3892/ol.2021.12777] [PMID: 33986876]
[http://dx.doi.org/10.1016/j.canlet.2017.04.032] [PMID: 28461246]
[http://dx.doi.org/10.3390/biomedicines10102512] [PMID: 36289774]
[PMID: 28820389]
[http://dx.doi.org/10.1186/1471-2407-13-349] [PMID: 23870412]
[http://dx.doi.org/10.1111/j.1349-7006.2010.01511.x] [PMID: 20219076]
[PMID: 24511017]
[PMID: 22993325]
[http://dx.doi.org/10.3389/fonc.2021.609743] [PMID: 33718163]
[http://dx.doi.org/10.1038/s41389-020-0220-5] [PMID: 32198343]
[http://dx.doi.org/10.1002/cncr.24495] [PMID: 19551889]
[http://dx.doi.org/10.1097/MPA.0000000000000867] [PMID: 28697132]
[http://dx.doi.org/10.1038/s41598-018-28928-3] [PMID: 30006603]
[http://dx.doi.org/10.3892/ol.2017.6852] [PMID: 29098035]
[http://dx.doi.org/10.1038/s41598-017-14539-x] [PMID: 29079854]
[http://dx.doi.org/10.1111/jop.12062] [PMID: 23551691]
[http://dx.doi.org/10.1016/j.canlet.2017.03.001] [PMID: 28279717]
[http://dx.doi.org/10.31557/APJCP.2020.21.11.3171] [PMID: 33247672]
[http://dx.doi.org/10.12659/MSM.904492] [PMID: 29079722]
[http://dx.doi.org/10.1038/onc.2014.5] [PMID: 24531710]
[http://dx.doi.org/10.1038/onc.2011.211] [PMID: 21643015]
[http://dx.doi.org/10.3892/mmr.2021.12022] [PMID: 33760220]
[http://dx.doi.org/10.1080/15384101.2017.1356508] [PMID: 28749195]
[http://dx.doi.org/10.2147/OTT.S217041] [PMID: 31807003]
[http://dx.doi.org/10.1091/mbc.E15-07-0456] [PMID: 26337386]
[http://dx.doi.org/10.1101/gad.192856.112] [PMID: 22677547]
[http://dx.doi.org/10.1126/science.1063443] [PMID: 11498579]
[http://dx.doi.org/10.1186/1471-2407-10-235] [PMID: 20504328]
[http://dx.doi.org/10.1186/s12885-020-06752-1] [PMID: 32245422]
[http://dx.doi.org/10.3892/ol.2016.4479] [PMID: 27284371]
[http://dx.doi.org/10.1345/aph.10365] [PMID: 11793628]
[http://dx.doi.org/10.1186/s12885-020-07555-0] [PMID: 33121449]
[http://dx.doi.org/10.1016/j.exer.2014.04.011] [PMID: 24837142]
[http://dx.doi.org/10.2174/0929867323666160316125048] [PMID: 26980565]
[http://dx.doi.org/10.1016/j.trecan.2019.04.001] [PMID: 31174842]
[http://dx.doi.org/10.1016/j.chembiol.2018.11.010] [PMID: 30581134]
[http://dx.doi.org/10.1016/j.canlet.2017.10.041] [PMID: 29097249]
[http://dx.doi.org/10.1186/s12967-019-1869-4] [PMID: 30961610]
[http://dx.doi.org/10.1038/s41420-018-0124-8] [PMID: 30479839]
[http://dx.doi.org/10.1016/j.jnutbio.2008.03.005] [PMID: 18656338]
[http://dx.doi.org/10.1016/j.str.2012.04.004] [PMID: 22632831]
[http://dx.doi.org/10.1016/j.ccr.2014.01.010] [PMID: 24525233]
[http://dx.doi.org/10.2147/JEP.S70568] [PMID: 28435333]
[http://dx.doi.org/10.3390/ijms150915173] [PMID: 25170806]