Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer
|
摘要
Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifica-tions, intera-ctions with coregula-tors, a-nd forma-tion of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.
Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifica-tions, intera-ctions with coregula-tors, a-nd forma-tion of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.
Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifica-tions, intera-ctions with coregula-tors, a-nd forma-tion of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.
引文
1 Germain P,Staels B,Dacquet C,Spedding M,Laudet V.Overview of nomenclature of nuclear receptors.Pharmacol Rev 2006;58:685-704[PMID:17132848 DOI:10.1124/pr.58.4.2]
2 Kumar R,Zakharov MN,Khan SH,Miki R,Jang H,Toraldo G,Singh R,Bhasin S,Jasuja R.The dynamic structure of the estrogen receptor.J Amino Acids 2011;2011:812540[PMID:22312471DOI:10.4061/2011/812540]
3 Ng HW,Perkins R,Tong W,Hong H.Versatility or promiscuity:the estrogen receptors,control of ligand selectivity and an update on subtype selective ligands.Int J Environ Res Public Health 2014;11:8709-8742[PMID:25162709 DOI:10.3390/ijerph110908709]
4 Manavathi B,Dey O,Gajulapalli VN,Bhatia RS,Bugide S,Kumar R.Derailed estrogen signaling and breast cancer:an au-thentic couple.Endocr Rev 2013;34:1-32[PMID:22947396 DOI:10.1210/er.2011-1057]
5 Vrta?nik P,Ostanek B,Mencej-Bedra?S,Marc J.The many faces of estrogen signaling.Biochem Med(Zagreb)2014;24:329-342[PMID:25351351 DOI:10.11613/BM.2014.035]
6 Hah N,Kraus WL.Hormone-regulated transcriptomes:lessons learned from estrogen signaling pathways in breast cancer cells.Mol Cell Endocrinol 2014;382:652-664[PMID:23810978 DOI:10.1016/j.mce.2013.06.021]
7 Hah N,Murakami S,Nagari A,Danko CG,Kraus WL.Enhancer transcripts mark active estrogen receptor binding sites.Genome Res 2013;23:1210-1223[PMID:23636943 DOI:10.1101/gr.152306.112]
8 Manavathi B,Samanthapudi VS,Gajulapalli VN.Estrogen re-ceptor coregulators and pioneer factors:the orchestrators of mam-mary gland cell fate and development.Front Cell Dev Biol 2014;2:34[PMID:25364741 DOI:10.3389/fcell.2014.00034]
9 Hervouet E,Cartron PF,Jouvenot M,Delage-Mourroux R.Epigenetic regulation of estrogen signaling in breast cancer.Epigenetics 2013;8:237-245[PMID:23364277 DOI:10.4161/epi.23790]
10 Rajbhandari P,Finn G,Solodin NM,Singarapu KK,Sahu SC,Markley JL,Kadunc KJ,Ellison-Zelski SJ,Kariagina A,Haslam SZ,Lu KP,Alarid ET.Regulation of estrogen receptorαN-terminus conformation and function by peptidyl prolyl isomerase Pin1.Mol Cell Biol 2012;32:445-457[PMID:22064478 DOI:10.1128/MCB.06073-11]
11 He C,Wang X,Zhang MQ.Nucleosome eviction and multiple co-factor binding predict estrogen-receptor-alpha-associated long-range interactions.Nucleic Acids Res 2014;42:6935-6944[PMID:24782518 DOI:10.1093/nar/gku327]
12 Liu MH,Cheung E.Estrogen receptor-mediated long-range chromatin interactions and transcription in breast cancer.Mol Cell Endocrinol 2014;382:624-632[PMID:24071518 DOI:10.1016/j.mce.2013.09.019]
13 Acconcia F,Kumar R.Signaling regulation of genomic and nongenomic functions of estrogen receptors.Cancer Lett 2006;238:1-14[PMID:16084012 DOI:10.1016/j.canlet.2005.06.018]
14 Kerdivel G,Flouriot G,Pakdel F.Modulation of estrogen receptor alpha activity and expression during breast cancer progression.Vitam Horm 2013;93:135-160[PMID:23810005 DOI:10.1016/B978-0-12-416673-8.00004-6]
15 Le Romancer M,Poulard C,Cohen P,Sentis S,Renoir JM,Corbo L.Cracking the estrogen receptor’s posttranslational code in breast tumors.Endocr Rev 2011;32:597-622[PMID:21680538 DOI:10.1210/er.2010-0016]
16 Soltysik K,Czekaj P.Membrane estrogen receptors-is it an alte-rnative way of estrogen action?J Physiol Pharmacol 2013;64:129-142[PMID:23756388]
17 Zhou W,Srinivasan S,Nawaz Z,Slingerland JM.ERα,SKP2 and E2F-1 form a feed forward loop driving late ERαtargets and G1cell cycle progression.Oncogene 2014;33:2341-2353[PMID:23770852 DOI:10.1038/onc.2013.197]
18 Trevi?o LS,Weigel NL.Phosphorylation:a fundamental regula-tor of steroid receptor action.Trends Endocrinol Metab 2013;24:515-524[PMID:23838532 DOI:10.1016/j.tem.2013.05.008]
19 Tecalco-Cruz AC,Pérez-Alvarado IA,Ramírez-Jarquín JO,Rocha-Zavaleta L.Nucleo-cytoplasmic transport of estrogen receptor alpha in breast cancer cells.Cell Signal 2017;34:121-132[PMID:28341599 DOI:10.1016/j.cellsig.2017.03.011]
20 Tecalco-Cruz AC,Ramírez-Jarquín JO.Mechanisms that Increase Stability of Estrogen Receptor Alpha in Breast Cancer.Clin Breast Cancer 2017;17:1-10[PMID:27561704 DOI:10.1016/j.clbc.2016.07.015]
21 Mohammed H,Russell IA,Stark R,Rueda OM,Hickey TE,Tarulli GA,Serandour AA,Birrell SN,Bruna A,Saadi A,Menon S,Hadfield J,Pugh M,Raj GV,Brown GD,D’Santos C,Robinson JL,Silva G,Launchbury R,Perou CM,Stingl J,Caldas C,Tilley WD,Carroll JS.Corrigendum:Progesterone receptor modulates ERαaction in breast cancer.Nature 2015;526:144[PMID:26245370 DOI:10.1038/nature14959]
22 Pedram A,Razandi M,Deschenes RJ,Levin ER.DHHC-7 and-21 are palmitoylacyltransferases for sex steroid receptors.Mol Biol Cell 2012;23:188-199[PMID:22031296 DOI:10.1091/mbc.E11-07-0638]
23 Acconcia F,Marino M.The Effects of 17β-estradiol in Cancer are Mediated by Estrogen Receptor Signaling at the Plasma Membrane.Front Physiol 2011;2:30[PMID:21747767 DOI:10.3389/fphys.2011.00030]
24 Marino M,Galluzzo P,Ascenzi P.Estrogen signaling multiple pathways to impact gene transcription.Curr Genomics 2006;7:497-508[PMID:18369406 DOI:10.2174/138920206779315737]
25 Miyoshi Y,Murase K,Saito M,Imamura M,Oh K.Mechanisms of estrogen receptor-αupregulation in breast cancers.Med Mol Morphol 2010;43:193-196[PMID:21267694 DOI:10.1007/s00795-010-0514-3]
26 Cook KL,Shajahan AN,Clarke R.Autophagy and endocrine re-sistance in breast cancer.Expert Rev Anticancer Ther 2011;11:1283-1294[PMID:21916582 DOI:10.1586/era.11.111]
27 Magnani L,Brunelle M,Gévry N,Lupien M.Chromatin landscape and endocrine response in breast cancer.Epigenomics 2012;4:675-683[PMID:23244312 DOI:10.2217/epi.12.64]
28 de Leeuw R,Neefjes J,Michalides R.A role for estrogen receptor phosphorylation in the resistance to tamoxifen.Int J Breast Cancer2011;2011:232435[PMID:22295213 DOI:10.4061/2011/232435]
29 Johnson AB,O’Malley BW.ERasing breast cancer resistance through the kinome.Nat Med 2011;17:660-661[PMID:21647142DOI:10.1038/nm0611-660]
30 Muluhngwi P,Klinge CM.Roles for mi RNAs in endocrine resistance in breast cancer.Endocr Relat Cancer 2015;22:R279-R300[PMID:26346768 DOI:10.1530/ERC-15-0355]
31 Osborne CK,Schiff R.Mechanisms of endocrine resistance in breast cancer.Annu Rev Med 2011;62:233-247[PMID:20887199DOI:10.1146/annurev-med-070909-182917]
32 Helzer KT,Hooper C,Miyamoto S,Alarid ET.Ubiquitylation of nuclear receptors:new linkages and therapeutic implications.J Mol Endocrinol 2015;54:R151-R167[PMID:25943391 DOI:10.1530/JME-14-0308]
33 Zhou W,Slingerland JM.Links between oestrogen receptor activation and proteolysis:relevance to hormone-regulated cancer therapy.Nat Rev Cancer 2014;14:26-38[PMID:24505618 DOI:10.1038/nrc3622]
34 Fan M,Park A,Nephew KP.CHIP(carboxyl terminus of Hsc70-interacting protein)promotes basal and geldanamycin-induced degradation of estrogen receptor-alpha.Mol Endocrinol 2005;19:2901-2914[PMID:16037132 DOI:10.1210/me.2005-0111]
35 Sun J,Zhou W,Kaliappan K,Nawaz Z,Slingerland JM.ERαphosphorylation at Y537 by Src triggers E6-AP-ERαbinding,ERαubiquitylation,promoter occupancy,and target gene expression.Mol Endocrinol 2012;26:1567-1577[PMID:22865929 DOI:10.1210/me.2012-1140]
36 Eakin CM,Maccoss MJ,Finney GL,Klevit RE.Estrogen receptor alpha is a putative substrate for the BRCA1 ubiquitin ligase.Proc Natl Acad Sci USA 2007;104:5794-5799[PMID:17392432 DOI:10.1073/pnas.0610887104]
37 Hashizume R,Fukuda M,Maeda I,Nishikawa H,Oyake D,Yabuki Y,Ogata H,Ohta T.The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation.J Biol Chem 2001;276:14537-14540[PMID:11278247 DOI:10.1074/jbc.C000881200]
38 Bhatt S,Xiao Z,Meng Z,Katzenellenbogen BS.Phosphorylation by p38 mitogen-activated protein kinase promotes estrogen receptorαturnover and functional activity via the SCF(Skp2)proteasomal complex.Mol Cell Biol 2012;32:1928-1943[PMID:22431515 DOI:10.1128/MCB.06561-11]
39 Saji S,Okumura N,Eguchi H,Nakashima S,Suzuki A,Toi M,Nozawa Y,Saji S,Hayashi S.MDM2 enhances the function of estrogen receptor alpha in human breast cancer cells.Biochem Biophys Res Commun 2001;281:259-265[PMID:11178989 DOI:10.1006/bbrc.2001.4339]
40 Iizuka M,Susa T,Tamamori-Adachi M,Okinaga H,Okazaki T.Intrinsic ubiquitin E3 ligase activity of histone acetyltransferase Hbo1 for estrogen receptorα.Proc Jpn Acad Ser B Phys Biol Sci2017;93:498-510[PMID:28769019 DOI:10.2183/pjab.93.030]
41 Kocanova S,Mazaheri M,Caze-Subra S,Bystricky K.Ligands specify estrogen receptor alpha nuclear localization and degradation.BMC Cell Biol 2010;11:98[PMID:21143970 DOI:10.1186/1471-2121-11-98]
42 Marsaud V,Gougelet A,Maillard S,Renoir JM.Various phosphorylation pathways,depending on agonist and antagonist binding to endogenous estrogen receptor alpha(ERalpha),differentially affect ERalpha extractability,proteasome-mediated stability,and transcriptional activity in human breast cancer cells.Mol Endocrinol 2003;17:2013-2027[PMID:12855746 DOI:10.1210/me.2002-0269]
43 Valley CC,Solodin NM,Powers GL,Ellison SJ,Alarid ET.Temporal variation in estrogen receptor-alpha protein turnover in the presence of estrogen.J Mol Endocrinol 2008;40:23-34[PMID:18096994DOI:10.1677/JME-07-0067]
44 Lonard DM,Nawaz Z,Smith CL,O’Malley BW.The 26Sproteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha transactivation.Mol Cell 2000;5:939-948[PMID:10911988 DOI:10.1016/S1097-2765(00)80259-2]
45 Reid G,Hübner MR,Métivier R,Brand H,Denger S,Manu D,Beaudouin J,Ellenberg J,Gannon F.Cyclic,proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling.Mol Cell2003;11:695-707[PMID:12667452 DOI:10.1016/S1097-2765(03)00090-X]
46 Berry NB,Fan M,Nephew KP.Estrogen receptor-alpha hinge-region lysines 302 and 303 regulate receptor degradation by the proteasome.Mol Endocrinol 2008;22:1535-1551[PMID:18388150 DOI:10.1210/me.2007-0449]
47 Wang Y,Zong H,Chi Y,Hong Y,Yang Y,Zou W,Yun X,Gu J.Repression of estrogen receptor alpha by CDK11p58 through promoting its ubiquitin-proteasome degradation.J Biochem 2009;145:331-343[PMID:19122208 DOI:10.1093/jb/mvn177]
48 Henrich LM,Smith JA,Kitt D,Errington TM,Nguyen B,Traish AM,Lannigan DA.Extracellular signal-regulated kinase 7,a regulator of hormone-dependent estrogen receptor destruction.Mol Cell Biol 2003;23:5979-5988[PMID:12917323 DOI:10.1128/MCB.23.17.5979-5988.2003]
49 Rajbhandari P,Schalper KA,Solodin NM,Ellison-Zelski SJ,Ping Lu K,Rimm DL,Alarid ET.Pin1 modulates ERαlevels in breast cancer through inhibition of phosphorylation-dependent ubiquitination and degradation.Oncogene 2014;33:1438-1447[PMID:23542176 DOI:10.1038/onc.2013.78]
50 Wei X,Xu H,Kufe D.MUC1 oncoprotein stabilizes and activates estrogen receptor alpha.Mol Cell 2006;21:295-305[PMID:16427018 DOI:10.1016/j.molcel.2005.11.030]
51 Ghosh SK,Uchida M,Yoo B,Ross AW,Gendler SJ,Gong J,Moore A,Medarova Z.Targeted imaging of breast tumor progression and therapeutic response in a human u MUC-1 expressing transgenic mouse model.Int J Cancer 2013;132:1860-1867[PMID:23015160 DOI:10.1002/ijc.27872]
52 Haddon L,Hugh J.MUC1-mediated motility in breast cancer:a review highlighting the role of the MUC1/ICAM-1/Src signaling triad.Clin Exp Metastasis 2015;32:393-403[PMID:25759211DOI:10.1007/s10585-015-9711-8]
53 Jin C,Rajabi H,Pitroda S,Li A,Kharbanda A,Weichselbaum R,Kufe D.Cooperative interaction between the MUC1-C oncoprotein and the Rab31 GTPase in estrogen receptor-positive breast cancer cells.PLo S One 2012;7:e39432[PMID:22792175 DOI:10.1371/journal.pone.0039432]
54 Raina D,Ahmad R,Joshi MD,Yin L,Wu Z,Kawano T,Vasir B,Avigan D,Kharbanda S,Kufe D.Direct targeting of the mucin1 oncoprotein blocks survival and tumorigenicity of human breast carcinoma cells.Cancer Res 2009;69:5133-5141[PMID:19491255 DOI:10.1158/0008-5472.CAN-09-0854]
55 Lu Z,Hunter T.Prolyl isomerase Pin1 in cancer.Cell Res 2014;24:1033-1049[PMID:25124924 DOI:10.1038/cr.2014.109]
56 Rajbhandari P,Ozers MS,Solodin NM,Warren CL,Alarid ET.Peptidylprolyl Isomerase Pin1 Directly Enhances the DNA Binding Functions of Estrogen Receptorα.J Biol Chem 2015;290:13749-13762[PMID:25866209 DOI:10.1074/jbc.M114.621698]
57 Wang JZ,Liu BG,Zhang Y.Pin1-based diagnostic and therapeutic strategies for breast cancer.Pharmacol Res 2015;93:28-35[PMID:25553719 DOI:10.1016/j.phrs.2014.12.005]
58 Giamas G,Filipovi?A,Jacob J,Messier W,Zhang H,Yang D,Zhang W,Shifa BA,Photiou A,Tralau-Stewart C,Castellano L,Green AR,Coombes RC,Ellis IO,Ali S,Lenz HJ,Stebbing J.Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer.Nat Med2011;17:715-719[PMID:21602804 DOI:10.1038/nm.2351]
59 Grisouard J,Medunjanin S,Hermani A,Shukla A,Mayer D.Glycogen synthase kinase-3 protects estrogen receptor alpha from proteasomal degradation and is required for full transcriptional activity of the receptor.Mol Endocrinol 2007;21:2427-2439[PMID:17609434 DOI:10.1210/me.2007-0129]
60 Medina M,Wandosell F.Deconstructing GSK-3:The Fine Regulation of Its Activity.Int J Alzheimers Dis 2011;2011:479249[PMID:21629747 DOI:10.4061/2011/479249]
61 Medunjanin S,Hermani A,De Servi B,Grisouard J,Rincke G,Mayer D.Glycogen synthase kinase-3 interacts with and phosphorylates estrogen receptor alpha and is involved in the regulation of receptor activity.J Biol Chem 2005;280:33006-33014[PMID:16076840DOI:10.1074/jbc.M506758200]
62 Dennis AP,Haq RU,Nawaz Z.Importance of the regulation of nuclear receptor degradation.Front Biosci 2001;6:D954-D959[PMID:11487464 DOI:10.2741/Dennis]
63 He X,Zheng Z,Song T,Wei C,Ma H,Ma Q,Zhang Y,Xu Y,Shi W,Ye Q,Zhong H.c-Abl regulates estrogen receptor alpha transcription activity through its stabilization by phosphorylation.Oncogene 2010;29:2238-2251[PMID:20101225 DOI:10.1038/onc.2009.513]
64 Caligiuri I,Toffoli G,Giordano A,Rizzolio F.p Rb controls estrogen receptor alpha protein stability and activity.Oncotarget 2013;4:875-883[PMID:23900261 DOI:10.18632/oncotarget.1036]
65 Zhu J,Zhao C,Kharman-Biz A,Zhuang T,Jonsson P,Liang N,Williams C,Lin CY,Qiao Y,Zendehdel K,Str?mblad S,Treuter E,Dahlman-Wright K.The atypical ubiquitin ligase RNF31 stabilizes estrogen receptorαand modulates estrogen-stimulated breast cancer cell proliferation.Oncogene 2014;33:4340-4351[PMID:24441041 DOI:10.1038/onc.2013.573]
66 Yang H,Yu N,Xu J,Ding X,Deng W,Wu G,Li X,Hou Y,Liu Z,Zhao Y,Xue M,Yu S,Wang B,Li X,Niu G,Wang H,Zhu J,Zhuang T.SMURF1 facilitates estrogen receptorɑsignaling in breast cancer cells.J Exp Clin Cancer Res 2018;37:24[PMID:29433542 DOI:10.1186/s13046-018-0672-z]
67 Zhuang T,Yu S,Zhang L,Yang H,Li X,Hou Y,Liu Z,Shi Y,Wang W,Yu N,Li A,Li X,Li X,Niu G,Xu J,Hasni MS,Mu K,Wang H,Zhu J.SHARPIN stabilizes estrogen receptorαand promotes breast cancer cell proliferation.Oncotarget 2017;8:77137-77151[PMID:29100376 DOI:10.18632/oncotarget.20368]
68 Wang S,Luo H,Wang C,Sun H,Sun G,Sun N,Zeng K,Song H,Zou R,Zhou T,Cong R,Liu W,Yang L,Li D,Zhou X,Zhong X,Lin L,Jiao J,Yan G,Wang X,Min X,Cao L,Zhao Y.RNF8identified as a co-activator of estrogen receptorαpromotes cell growth in breast cancer.Biochim Biophys Acta 2017;1863:1615-1628[PMID:28216286 DOI:10.1016/j.bbadis.2017.02.011]
69 Chai F,Liang Y,Bi J,Chen L,Zhang F,Cui Y,Jiang J.REGγregulates ERαdegradation via ubiquitin-proteasome pathway in breast cancer.Biochem Biophys Res Commun 2015;456:534-540[PMID:25490392 DOI:10.1016/j.bbrc.2014.11.124]
70 Liu H,Qiu J,Li N,Chen T,Cao X.Human phosphatidylethanolamine-binding protein 4 promotes transactivation of estrogen receptor alpha(ERalpha)in human cancer cells by inhibiting proteasome-dependent ERalpha degradation via association with Src.J Biol Chem 2010;285:21934-21942[PMID:20460377 DOI:10.1074/jbc.M110.109876]
71 Kim SH,Kang HJ,Na H,Lee MO.Trichostatin A enhances acetylation as well as protein stability of ERalpha through induction of p300 protein.Breast Cancer Res 2010;12:R22[PMID:20388208DOI:10.1186/bcr2562]
72 La Rosa P,Pesiri V,Leclercq G,Marino M,Acconcia F.Palmitoylation regulates 17β-estradiol-induced estrogen receptor-αdegradation and transcriptional activity.Mol Endocrinol 2012;26:762-774[PMID:22446104 DOI:10.1210/me.2011-1208]
73 Murphy LC,Seekallu SV,Watson PH.Clinical significance of estrogen receptor phosphorylation.Endocr Relat Cancer 2011;18:R1-14[PMID:21149515 DOI:10.1677/ERC-10-0070]
74 Thomas C,Gustafsson J?.Estrogen receptor mutations and functional consequences for breast cancer.Trends Endocrinol Metab 2015;26:467-476[PMID:26183887 DOI:10.1016/j.tem.2015.06.007]
75 Yeh WL,Shioda K,Coser KR,Rivizzigno D,Mc Sweeney KR,Shioda T.Fulvestrant-induced cell death and proteasomal degradation of estrogen receptorαprotein in MCF-7 cells require the CSK c-Src tyrosine kinase.PLo S One 2013;8:e60889[PMID:23593342 DOI:10.1371/journal.pone.0060889]
76 De Savi C,Bradbury RH,Rabow AA,Norman RA,Buttar D,Currie GS,Weir H,Donald C,Andrews D,Mac Faul P,Ballard P,Curwen J,Wilson Z,Richmond G,D’Cruz C,Powell S,Walker G,Hulse M,Tonge M.Abstract 3650:Discovery of the clinical candidate AZD9496:a potent and orally bioavailable selective estrogen receptor downregulator and antagonist.Cancer Research2015;75:3650[DOI:10.1158/1538-7445.AM2015-3650]
77 Lai A,Kahraman M,Govek S,Nagasawa J,Bonnefous C,Julien J,Douglas K,Sensintaffar J,Lu N,Lee KJ,Aparicio A,Kaufman J,Qian J,Shao G,Prudente R,Moon MJ,Joseph JD,Darimont B,Brigham D,Grillot K,Heyman R,Rix PJ,Hager JH,Smith ND.Identification of GDC-0810(ARN-810),an Orally Bioavailable Selective Estrogen Receptor Degrader(SERD)that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.J Med Chem 2015;58:4888-4904[PMID:25879485 DOI:10.1021/acs.jmedchem.5b00054]
78 Wardell SE,Nelson ER,Chao CA,Mc Donnell DP.Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen-resistant breast cancer:implications for treatment of advanced disease.Clin Cancer Res 2013;19:2420-2431[PMID:23536434DOI:10.1158/1078-0432.CCR-12-3771]
79 Garner F,Shomali M,Paquin D,Lyttle CR,Hattersley G.RAD1901:a novel,orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models.Anticancer Drugs 2015;26:948-956[PMID:26164151 DOI:10.1097/CAD.0000000000000271]
80 Kim JA,Kim MR,Kim O,Phuong NT,Yun J,Oh WK,Bae K,Kang KW.Amurensin G inhibits angiogenesis and tumor growth of tamoxifen-resistant breast cancer via Pin1 inhibition.Food Chem Toxicol 2012;50:3625-3634[PMID:22842120 DOI:10.1016/j.fct.2012.07.027]
81 Kim JH,Jung JH,Kim SH,Jeong SJ.Decursin exerts anti-cancer activity in MDA-MB-231 breast cancer cells via inhibition of the Pin1 activity and enhancement of the Pin1/p53 association.Phytother Res 2014;28:238-244[PMID:23580332 DOI:10.1002/ptr.4986]
82 Kotiyal S,Bhattacharya S.Breast cancer stem cells,EMT and therapeutic targets.Biochem Biophys Res Commun 2014;453:112-116[PMID:25261721 DOI:10.1016/j.bbrc.2014.09.069]
83 Li X,Li L,Zhou Q,Zhang N,Zhang S,Zhao R,Liu D,Jing Y,Zhao L.Synthesis of the novel elemonic acid derivatives as Pin1inhibitors.Bioorg Med Chem Lett 2014;24:5612-5615[PMID:25466185 DOI:10.1016/j.bmcl.2014.10.087]
84 Moore JD,Potter A.Pin1 inhibitors:Pitfalls,progress and cellular pharmacology.Bioorg Med Chem Lett 2013;23:4283-4291[PMID:23796453 DOI:10.1016/j.bmcl.2013.05.088]
85 Potter A,Oldfield V,Nunns C,Fromont C,Ray S,Northfield CJ,Bryant CJ,Scrace SF,Robinson D,Matossova N,Baker L,Dokurno P,Surgenor AE,Davis B,Richardson CM,Murray JB,Moore JD.Discovery of cell-active phenyl-imidazole Pin1inhibitors by structure-guided fragment evolution.Bioorg Med Chem Lett 2010;20:6483-6488[PMID:20932746 DOI:10.1016/j.bmcl.2010.09.063]
86 Wei S,Kozono S,Kats L,Nechama M,Li W,Guarnerio J,Luo M,You MH,Yao Y,Kondo A,Hu H,Bozkurt G,Moerke NJ,Cao S,Reschke M,Chen CH,Rego EM,Lo-Coco F,Cantley LC,Lee TH,Wu H,Zhang Y,Pandolfi PP,Zhou XZ,Lu KP.Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer.Nat Med 2015;21:457-466[PMID:25849135DOI:10.1038/nm.3839]
87 Xu GG,Slebodnick C,Etzkorn FA.Cyclohexyl ketone inhibitors of Pin1 dock in a trans-diaxial cyclohexane conformation.PLo SOne 2012;7:e44226[PMID:23028504 DOI:10.1371/journal.pone.0044226]
88 Stebbing J,Filipovic A,Ellis IO,Green AR,D’Silva TR,Lenz HJ,Coombes RC,Wang T,Lee SC,Giamas G.LMTK3 expression in breast cancer:association with tumor phenotype and clinical outcome.Breast Cancer Res Treat 2012;132:537-544[PMID:21671015 DOI:10.1007/s10549-011-1622-z]
89 Stebbing J,Filipovic A,Lit LC,Blighe K,Grothey A,Xu Y,Miki Y,Chow LW,Coombes RC,Sasano H,Shaw JA,Giamas G.LMTK3is implicated in endocrine resistance via multiple signaling pathways.Oncogene 2013;32:3371-3380[PMID:22869149 DOI:10.1038/onc.2012.343]
90 Zhao G,Guo J,Li D,Jia C,Yin W,Sun R,Lv Z,Cong X.Micro RNA-34a suppresses cell proliferation by targeting LMTK3in human breast cancer mcf-7 cell line.DNA Cell Biol 2013;32:699-707[PMID:24050776 DOI:10.1089/dna.2013.2130]
91 Jacobs KM,Bhave SR,Ferraro DJ,Jaboin JJ,Hallahan DE,Thotala D.GSK-3β:A Bifunctional Role in Cell Death Pathways.Int J Cell Biol 2012;2012:930710[PMID:22675363 DOI:10.1155/2012/930710]
92 Kim HM,Kim CS,Lee JH,Jang SJ,Hwang JJ,Ro S,Choi J.CG0009,a novel glycogen synthase kinase 3 inhibitor,induces cell death through cyclin D1 depletion in breast cancer cells.PLo SOne 2013;8:e60383[PMID:23565238 DOI:10.1371/journal.pone.0060383]
93 Mc Cubrey JA,Davis NM,Abrams SL,Montalto G,Cervello M,Basecke J,Libra M,Nicoletti F,Cocco L,Martelli AM,Steelman LS.Diverse roles of GSK-3:tumor promoter-tumor suppressor,target in cancer therapy.Adv Biol Regul 2014;54:176-196[PMID:24169510 DOI:10.1016/j.jbior.2013.09.013]
94 Mishra R.Glycogen synthase kinase 3 beta:can it be a target for oral cancer.Mol Cancer 2010;9:144[PMID:20537194 DOI:10.1186/1476-4598-9-144]
95 Ertel A,Dean JL,Rui H,Liu C,Witkiewicz AK,Knudsen KE,Knudsen ES.RB-pathway disruption in breast cancer:differential association with disease subtypes,disease-specific prognosis and therapeutic response.Cell Cycle 2010;9:4153-4163[PMID:20948315 DOI:10.4161/cc.9.20.13454]
96 Lehn S,Fern?M,Jirstr?m K,Rydén L,Landberg G.A non-functional retinoblastoma tumor suppressor(RB)pathway in premenopausal breast cancer is associated with resistance to tamoxifen.Cell Cycle2011;10:956-962[PMID:21358261 DOI:10.4161/cc.10.6.15074]
97 TreréD,Brighenti E,Donati G,Ceccarelli C,Santini D,Taffurelli M,Montanaro L,Derenzini M.High prevalence of retinoblastoma protein loss in triple-negative breast cancers and its association with a good prognosis in patients treated with adjuvant chemotherapy.Ann Oncol 2009;20:1818-1823[PMID:19556322 DOI:10.1093/annonc/mdp209]
98 Witkiewicz AK,Knudsen ES.Retinoblastoma tumor suppressor pathway in breast cancer:prognosis,precision medicine,and therapeutic interventions.Breast Cancer Res 2014;16:207[PMID:25223380 DOI:10.1186/bcr3652]
99 Alam M,Rajabi H,Ahmad R,Jin C,Kufe D.Targeting the MUC1-Concoprotein inhibits self-renewal capacity of breast cancer cells.Oncotarget 2014;5:2622-2634[PMID:24770886 DOI:10.18632/oncotarget.1848]
100 Kharbanda A,Rajabi H,Jin C,Raina D,Kufe D.Oncogenic MUC1-C promotes tamoxifen resistance in human breast cancer.Mol Cancer Res 2013;11:714-723[PMID:23538857 DOI:10.1158/1541-7786.MCR-12-0668]
101 Pitroda SP,Khodarev NN,Beckett MA,Kufe DW,Weichselbaum RR.MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment.Proc Natl Acad Sci USA 2009;106:5837-5841[PMID:19289846DOI:10.1073/pnas.0812029106]
102 Alam M,Bouillez A,Tagde A,Ahmad R,Rajabi H,Maeda T,Hiraki M,Suzuki Y,Kufe D.MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway.Mol Cancer Res 2016;14:1266-1276[PMID:27658423DOI:10.1158/1541-7786.MCR-16-0233]
103 Jin C,Rajabi H,Kufe D.mi R-1226 targets expression of the mucin 1 oncoprotein and induces cell death.Int J Oncol 2010;37:61-69[PMID:20514397]
104 Sachdeva M,Mo YY.Micro RNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1.Cancer Res 2010;70:378-387[PMID:19996288 DOI:10.1158/0008-5472.CAN-09-2021]
105 Lacunza E,Baudis M,Colussi AG,Segal-Eiras A,Croce MV,Abba MC.MUC1 oncogene amplification correlates with protein overexpression in invasive breast carcinoma cells.Cancer Genet Cytogenet 2010;201:102-110[PMID:20682394 DOI:10.1016/j.cancergencyto.2010.05.015]
106 Rajabi H,Jin C,Ahmad R,Mc Clary C,Joshi MD,Kufe D.MUCIN 1 ONCOPROTEIN EXPRESSION IS SUPPRESSED BYTHE mi R-125b ONCOMIR.Genes Cancer 2010;1:62-68[PMID:20729973 DOI:10.1177/1947601909357933]
107 Zhou Y,Rajabi H,Kufe D.Mucin 1 C-terminal subunit oncoprotein is a target for small-molecule inhibitors.Mol Pharmacol 2011;79:886-893[PMID:21346142 DOI:10.1124/mol.110.070797]
108 Yuan S,Shi C,Ling R,Wang T,Wang H,Han W.Immunization with two recombinant Bacillus Calmette-Guérin vaccines that combine the expression of multiple tandem repeats of mucin-1 and colony stimulating-factor suppress breast tumor growth in mice.JCancer Res Clin Oncol 2010;136:1359-1367[PMID:20127358DOI:10.1007/s00432-010-0787-x]
109 Yuan S,Shi C,Liu L,Han W.MUC1-based recombinant Bacillus Calmette-Guerin vaccines as candidates for breast cancer immuno-therapy.Expert Opin Biol Ther 2010;10:1037-1048[PMID:20420512DOI:10.1517/14712598.2010.485185]
110 Kotzsch M,Kirchner T,Soelch S,Sch?fer S,Friedrich K,Baretton G,Magdolen V,Luther T.Inverse association of rab31 and mucin-1(CA15-3)antigen levels in estrogen receptor-positive(ER+)breast cancer tissues with clinicopathological parameters and patients’prognosis.Am J Cancer Res 2017;7:1959-1970[PMID:28979817]
111 Fowler AM,Solodin N,Preisler-Mashek MT,Zhang P,Lee AV,Alarid ET.Increases in estrogen receptor-alpha concentration in breast cancer cells promote serine 118/104/106-independent AF-1transactivation and growth in the absence of estrogen.FASEB J2004;18:81-93[PMID:14718389 DOI:10.1096/fj.03-0038com]
112 Fowler AM,Solodin NM,Valley CC,Alarid ET.Altered target gene regulation controlled by estrogen receptor-alpha concentration.Mol Endocrinol 2006;20:291-301[PMID:16179380 DOI:10.1210/me.2005-0288]
2 Kumar R,Zakharov MN,Khan SH,Miki R,Jang H,Toraldo G,Singh R,Bhasin S,Jasuja R.The dynamic structure of the estrogen receptor.J Amino Acids 2011;2011:812540[PMID:22312471DOI:10.4061/2011/812540]
3 Ng HW,Perkins R,Tong W,Hong H.Versatility or promiscuity:the estrogen receptors,control of ligand selectivity and an update on subtype selective ligands.Int J Environ Res Public Health 2014;11:8709-8742[PMID:25162709 DOI:10.3390/ijerph110908709]
4 Manavathi B,Dey O,Gajulapalli VN,Bhatia RS,Bugide S,Kumar R.Derailed estrogen signaling and breast cancer:an au-thentic couple.Endocr Rev 2013;34:1-32[PMID:22947396 DOI:10.1210/er.2011-1057]
5 Vrta?nik P,Ostanek B,Mencej-Bedra?S,Marc J.The many faces of estrogen signaling.Biochem Med(Zagreb)2014;24:329-342[PMID:25351351 DOI:10.11613/BM.2014.035]
6 Hah N,Kraus WL.Hormone-regulated transcriptomes:lessons learned from estrogen signaling pathways in breast cancer cells.Mol Cell Endocrinol 2014;382:652-664[PMID:23810978 DOI:10.1016/j.mce.2013.06.021]
7 Hah N,Murakami S,Nagari A,Danko CG,Kraus WL.Enhancer transcripts mark active estrogen receptor binding sites.Genome Res 2013;23:1210-1223[PMID:23636943 DOI:10.1101/gr.152306.112]
8 Manavathi B,Samanthapudi VS,Gajulapalli VN.Estrogen re-ceptor coregulators and pioneer factors:the orchestrators of mam-mary gland cell fate and development.Front Cell Dev Biol 2014;2:34[PMID:25364741 DOI:10.3389/fcell.2014.00034]
9 Hervouet E,Cartron PF,Jouvenot M,Delage-Mourroux R.Epigenetic regulation of estrogen signaling in breast cancer.Epigenetics 2013;8:237-245[PMID:23364277 DOI:10.4161/epi.23790]
10 Rajbhandari P,Finn G,Solodin NM,Singarapu KK,Sahu SC,Markley JL,Kadunc KJ,Ellison-Zelski SJ,Kariagina A,Haslam SZ,Lu KP,Alarid ET.Regulation of estrogen receptorαN-terminus conformation and function by peptidyl prolyl isomerase Pin1.Mol Cell Biol 2012;32:445-457[PMID:22064478 DOI:10.1128/MCB.06073-11]
11 He C,Wang X,Zhang MQ.Nucleosome eviction and multiple co-factor binding predict estrogen-receptor-alpha-associated long-range interactions.Nucleic Acids Res 2014;42:6935-6944[PMID:24782518 DOI:10.1093/nar/gku327]
12 Liu MH,Cheung E.Estrogen receptor-mediated long-range chromatin interactions and transcription in breast cancer.Mol Cell Endocrinol 2014;382:624-632[PMID:24071518 DOI:10.1016/j.mce.2013.09.019]
13 Acconcia F,Kumar R.Signaling regulation of genomic and nongenomic functions of estrogen receptors.Cancer Lett 2006;238:1-14[PMID:16084012 DOI:10.1016/j.canlet.2005.06.018]
14 Kerdivel G,Flouriot G,Pakdel F.Modulation of estrogen receptor alpha activity and expression during breast cancer progression.Vitam Horm 2013;93:135-160[PMID:23810005 DOI:10.1016/B978-0-12-416673-8.00004-6]
15 Le Romancer M,Poulard C,Cohen P,Sentis S,Renoir JM,Corbo L.Cracking the estrogen receptor’s posttranslational code in breast tumors.Endocr Rev 2011;32:597-622[PMID:21680538 DOI:10.1210/er.2010-0016]
16 Soltysik K,Czekaj P.Membrane estrogen receptors-is it an alte-rnative way of estrogen action?J Physiol Pharmacol 2013;64:129-142[PMID:23756388]
17 Zhou W,Srinivasan S,Nawaz Z,Slingerland JM.ERα,SKP2 and E2F-1 form a feed forward loop driving late ERαtargets and G1cell cycle progression.Oncogene 2014;33:2341-2353[PMID:23770852 DOI:10.1038/onc.2013.197]
18 Trevi?o LS,Weigel NL.Phosphorylation:a fundamental regula-tor of steroid receptor action.Trends Endocrinol Metab 2013;24:515-524[PMID:23838532 DOI:10.1016/j.tem.2013.05.008]
19 Tecalco-Cruz AC,Pérez-Alvarado IA,Ramírez-Jarquín JO,Rocha-Zavaleta L.Nucleo-cytoplasmic transport of estrogen receptor alpha in breast cancer cells.Cell Signal 2017;34:121-132[PMID:28341599 DOI:10.1016/j.cellsig.2017.03.011]
20 Tecalco-Cruz AC,Ramírez-Jarquín JO.Mechanisms that Increase Stability of Estrogen Receptor Alpha in Breast Cancer.Clin Breast Cancer 2017;17:1-10[PMID:27561704 DOI:10.1016/j.clbc.2016.07.015]
21 Mohammed H,Russell IA,Stark R,Rueda OM,Hickey TE,Tarulli GA,Serandour AA,Birrell SN,Bruna A,Saadi A,Menon S,Hadfield J,Pugh M,Raj GV,Brown GD,D’Santos C,Robinson JL,Silva G,Launchbury R,Perou CM,Stingl J,Caldas C,Tilley WD,Carroll JS.Corrigendum:Progesterone receptor modulates ERαaction in breast cancer.Nature 2015;526:144[PMID:26245370 DOI:10.1038/nature14959]
22 Pedram A,Razandi M,Deschenes RJ,Levin ER.DHHC-7 and-21 are palmitoylacyltransferases for sex steroid receptors.Mol Biol Cell 2012;23:188-199[PMID:22031296 DOI:10.1091/mbc.E11-07-0638]
23 Acconcia F,Marino M.The Effects of 17β-estradiol in Cancer are Mediated by Estrogen Receptor Signaling at the Plasma Membrane.Front Physiol 2011;2:30[PMID:21747767 DOI:10.3389/fphys.2011.00030]
24 Marino M,Galluzzo P,Ascenzi P.Estrogen signaling multiple pathways to impact gene transcription.Curr Genomics 2006;7:497-508[PMID:18369406 DOI:10.2174/138920206779315737]
25 Miyoshi Y,Murase K,Saito M,Imamura M,Oh K.Mechanisms of estrogen receptor-αupregulation in breast cancers.Med Mol Morphol 2010;43:193-196[PMID:21267694 DOI:10.1007/s00795-010-0514-3]
26 Cook KL,Shajahan AN,Clarke R.Autophagy and endocrine re-sistance in breast cancer.Expert Rev Anticancer Ther 2011;11:1283-1294[PMID:21916582 DOI:10.1586/era.11.111]
27 Magnani L,Brunelle M,Gévry N,Lupien M.Chromatin landscape and endocrine response in breast cancer.Epigenomics 2012;4:675-683[PMID:23244312 DOI:10.2217/epi.12.64]
28 de Leeuw R,Neefjes J,Michalides R.A role for estrogen receptor phosphorylation in the resistance to tamoxifen.Int J Breast Cancer2011;2011:232435[PMID:22295213 DOI:10.4061/2011/232435]
29 Johnson AB,O’Malley BW.ERasing breast cancer resistance through the kinome.Nat Med 2011;17:660-661[PMID:21647142DOI:10.1038/nm0611-660]
30 Muluhngwi P,Klinge CM.Roles for mi RNAs in endocrine resistance in breast cancer.Endocr Relat Cancer 2015;22:R279-R300[PMID:26346768 DOI:10.1530/ERC-15-0355]
31 Osborne CK,Schiff R.Mechanisms of endocrine resistance in breast cancer.Annu Rev Med 2011;62:233-247[PMID:20887199DOI:10.1146/annurev-med-070909-182917]
32 Helzer KT,Hooper C,Miyamoto S,Alarid ET.Ubiquitylation of nuclear receptors:new linkages and therapeutic implications.J Mol Endocrinol 2015;54:R151-R167[PMID:25943391 DOI:10.1530/JME-14-0308]
33 Zhou W,Slingerland JM.Links between oestrogen receptor activation and proteolysis:relevance to hormone-regulated cancer therapy.Nat Rev Cancer 2014;14:26-38[PMID:24505618 DOI:10.1038/nrc3622]
34 Fan M,Park A,Nephew KP.CHIP(carboxyl terminus of Hsc70-interacting protein)promotes basal and geldanamycin-induced degradation of estrogen receptor-alpha.Mol Endocrinol 2005;19:2901-2914[PMID:16037132 DOI:10.1210/me.2005-0111]
35 Sun J,Zhou W,Kaliappan K,Nawaz Z,Slingerland JM.ERαphosphorylation at Y537 by Src triggers E6-AP-ERαbinding,ERαubiquitylation,promoter occupancy,and target gene expression.Mol Endocrinol 2012;26:1567-1577[PMID:22865929 DOI:10.1210/me.2012-1140]
36 Eakin CM,Maccoss MJ,Finney GL,Klevit RE.Estrogen receptor alpha is a putative substrate for the BRCA1 ubiquitin ligase.Proc Natl Acad Sci USA 2007;104:5794-5799[PMID:17392432 DOI:10.1073/pnas.0610887104]
37 Hashizume R,Fukuda M,Maeda I,Nishikawa H,Oyake D,Yabuki Y,Ogata H,Ohta T.The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation.J Biol Chem 2001;276:14537-14540[PMID:11278247 DOI:10.1074/jbc.C000881200]
38 Bhatt S,Xiao Z,Meng Z,Katzenellenbogen BS.Phosphorylation by p38 mitogen-activated protein kinase promotes estrogen receptorαturnover and functional activity via the SCF(Skp2)proteasomal complex.Mol Cell Biol 2012;32:1928-1943[PMID:22431515 DOI:10.1128/MCB.06561-11]
39 Saji S,Okumura N,Eguchi H,Nakashima S,Suzuki A,Toi M,Nozawa Y,Saji S,Hayashi S.MDM2 enhances the function of estrogen receptor alpha in human breast cancer cells.Biochem Biophys Res Commun 2001;281:259-265[PMID:11178989 DOI:10.1006/bbrc.2001.4339]
40 Iizuka M,Susa T,Tamamori-Adachi M,Okinaga H,Okazaki T.Intrinsic ubiquitin E3 ligase activity of histone acetyltransferase Hbo1 for estrogen receptorα.Proc Jpn Acad Ser B Phys Biol Sci2017;93:498-510[PMID:28769019 DOI:10.2183/pjab.93.030]
41 Kocanova S,Mazaheri M,Caze-Subra S,Bystricky K.Ligands specify estrogen receptor alpha nuclear localization and degradation.BMC Cell Biol 2010;11:98[PMID:21143970 DOI:10.1186/1471-2121-11-98]
42 Marsaud V,Gougelet A,Maillard S,Renoir JM.Various phosphorylation pathways,depending on agonist and antagonist binding to endogenous estrogen receptor alpha(ERalpha),differentially affect ERalpha extractability,proteasome-mediated stability,and transcriptional activity in human breast cancer cells.Mol Endocrinol 2003;17:2013-2027[PMID:12855746 DOI:10.1210/me.2002-0269]
43 Valley CC,Solodin NM,Powers GL,Ellison SJ,Alarid ET.Temporal variation in estrogen receptor-alpha protein turnover in the presence of estrogen.J Mol Endocrinol 2008;40:23-34[PMID:18096994DOI:10.1677/JME-07-0067]
44 Lonard DM,Nawaz Z,Smith CL,O’Malley BW.The 26Sproteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha transactivation.Mol Cell 2000;5:939-948[PMID:10911988 DOI:10.1016/S1097-2765(00)80259-2]
45 Reid G,Hübner MR,Métivier R,Brand H,Denger S,Manu D,Beaudouin J,Ellenberg J,Gannon F.Cyclic,proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling.Mol Cell2003;11:695-707[PMID:12667452 DOI:10.1016/S1097-2765(03)00090-X]
46 Berry NB,Fan M,Nephew KP.Estrogen receptor-alpha hinge-region lysines 302 and 303 regulate receptor degradation by the proteasome.Mol Endocrinol 2008;22:1535-1551[PMID:18388150 DOI:10.1210/me.2007-0449]
47 Wang Y,Zong H,Chi Y,Hong Y,Yang Y,Zou W,Yun X,Gu J.Repression of estrogen receptor alpha by CDK11p58 through promoting its ubiquitin-proteasome degradation.J Biochem 2009;145:331-343[PMID:19122208 DOI:10.1093/jb/mvn177]
48 Henrich LM,Smith JA,Kitt D,Errington TM,Nguyen B,Traish AM,Lannigan DA.Extracellular signal-regulated kinase 7,a regulator of hormone-dependent estrogen receptor destruction.Mol Cell Biol 2003;23:5979-5988[PMID:12917323 DOI:10.1128/MCB.23.17.5979-5988.2003]
49 Rajbhandari P,Schalper KA,Solodin NM,Ellison-Zelski SJ,Ping Lu K,Rimm DL,Alarid ET.Pin1 modulates ERαlevels in breast cancer through inhibition of phosphorylation-dependent ubiquitination and degradation.Oncogene 2014;33:1438-1447[PMID:23542176 DOI:10.1038/onc.2013.78]
50 Wei X,Xu H,Kufe D.MUC1 oncoprotein stabilizes and activates estrogen receptor alpha.Mol Cell 2006;21:295-305[PMID:16427018 DOI:10.1016/j.molcel.2005.11.030]
51 Ghosh SK,Uchida M,Yoo B,Ross AW,Gendler SJ,Gong J,Moore A,Medarova Z.Targeted imaging of breast tumor progression and therapeutic response in a human u MUC-1 expressing transgenic mouse model.Int J Cancer 2013;132:1860-1867[PMID:23015160 DOI:10.1002/ijc.27872]
52 Haddon L,Hugh J.MUC1-mediated motility in breast cancer:a review highlighting the role of the MUC1/ICAM-1/Src signaling triad.Clin Exp Metastasis 2015;32:393-403[PMID:25759211DOI:10.1007/s10585-015-9711-8]
53 Jin C,Rajabi H,Pitroda S,Li A,Kharbanda A,Weichselbaum R,Kufe D.Cooperative interaction between the MUC1-C oncoprotein and the Rab31 GTPase in estrogen receptor-positive breast cancer cells.PLo S One 2012;7:e39432[PMID:22792175 DOI:10.1371/journal.pone.0039432]
54 Raina D,Ahmad R,Joshi MD,Yin L,Wu Z,Kawano T,Vasir B,Avigan D,Kharbanda S,Kufe D.Direct targeting of the mucin1 oncoprotein blocks survival and tumorigenicity of human breast carcinoma cells.Cancer Res 2009;69:5133-5141[PMID:19491255 DOI:10.1158/0008-5472.CAN-09-0854]
55 Lu Z,Hunter T.Prolyl isomerase Pin1 in cancer.Cell Res 2014;24:1033-1049[PMID:25124924 DOI:10.1038/cr.2014.109]
56 Rajbhandari P,Ozers MS,Solodin NM,Warren CL,Alarid ET.Peptidylprolyl Isomerase Pin1 Directly Enhances the DNA Binding Functions of Estrogen Receptorα.J Biol Chem 2015;290:13749-13762[PMID:25866209 DOI:10.1074/jbc.M114.621698]
57 Wang JZ,Liu BG,Zhang Y.Pin1-based diagnostic and therapeutic strategies for breast cancer.Pharmacol Res 2015;93:28-35[PMID:25553719 DOI:10.1016/j.phrs.2014.12.005]
58 Giamas G,Filipovi?A,Jacob J,Messier W,Zhang H,Yang D,Zhang W,Shifa BA,Photiou A,Tralau-Stewart C,Castellano L,Green AR,Coombes RC,Ellis IO,Ali S,Lenz HJ,Stebbing J.Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer.Nat Med2011;17:715-719[PMID:21602804 DOI:10.1038/nm.2351]
59 Grisouard J,Medunjanin S,Hermani A,Shukla A,Mayer D.Glycogen synthase kinase-3 protects estrogen receptor alpha from proteasomal degradation and is required for full transcriptional activity of the receptor.Mol Endocrinol 2007;21:2427-2439[PMID:17609434 DOI:10.1210/me.2007-0129]
60 Medina M,Wandosell F.Deconstructing GSK-3:The Fine Regulation of Its Activity.Int J Alzheimers Dis 2011;2011:479249[PMID:21629747 DOI:10.4061/2011/479249]
61 Medunjanin S,Hermani A,De Servi B,Grisouard J,Rincke G,Mayer D.Glycogen synthase kinase-3 interacts with and phosphorylates estrogen receptor alpha and is involved in the regulation of receptor activity.J Biol Chem 2005;280:33006-33014[PMID:16076840DOI:10.1074/jbc.M506758200]
62 Dennis AP,Haq RU,Nawaz Z.Importance of the regulation of nuclear receptor degradation.Front Biosci 2001;6:D954-D959[PMID:11487464 DOI:10.2741/Dennis]
63 He X,Zheng Z,Song T,Wei C,Ma H,Ma Q,Zhang Y,Xu Y,Shi W,Ye Q,Zhong H.c-Abl regulates estrogen receptor alpha transcription activity through its stabilization by phosphorylation.Oncogene 2010;29:2238-2251[PMID:20101225 DOI:10.1038/onc.2009.513]
64 Caligiuri I,Toffoli G,Giordano A,Rizzolio F.p Rb controls estrogen receptor alpha protein stability and activity.Oncotarget 2013;4:875-883[PMID:23900261 DOI:10.18632/oncotarget.1036]
65 Zhu J,Zhao C,Kharman-Biz A,Zhuang T,Jonsson P,Liang N,Williams C,Lin CY,Qiao Y,Zendehdel K,Str?mblad S,Treuter E,Dahlman-Wright K.The atypical ubiquitin ligase RNF31 stabilizes estrogen receptorαand modulates estrogen-stimulated breast cancer cell proliferation.Oncogene 2014;33:4340-4351[PMID:24441041 DOI:10.1038/onc.2013.573]
66 Yang H,Yu N,Xu J,Ding X,Deng W,Wu G,Li X,Hou Y,Liu Z,Zhao Y,Xue M,Yu S,Wang B,Li X,Niu G,Wang H,Zhu J,Zhuang T.SMURF1 facilitates estrogen receptorɑsignaling in breast cancer cells.J Exp Clin Cancer Res 2018;37:24[PMID:29433542 DOI:10.1186/s13046-018-0672-z]
67 Zhuang T,Yu S,Zhang L,Yang H,Li X,Hou Y,Liu Z,Shi Y,Wang W,Yu N,Li A,Li X,Li X,Niu G,Xu J,Hasni MS,Mu K,Wang H,Zhu J.SHARPIN stabilizes estrogen receptorαand promotes breast cancer cell proliferation.Oncotarget 2017;8:77137-77151[PMID:29100376 DOI:10.18632/oncotarget.20368]
68 Wang S,Luo H,Wang C,Sun H,Sun G,Sun N,Zeng K,Song H,Zou R,Zhou T,Cong R,Liu W,Yang L,Li D,Zhou X,Zhong X,Lin L,Jiao J,Yan G,Wang X,Min X,Cao L,Zhao Y.RNF8identified as a co-activator of estrogen receptorαpromotes cell growth in breast cancer.Biochim Biophys Acta 2017;1863:1615-1628[PMID:28216286 DOI:10.1016/j.bbadis.2017.02.011]
69 Chai F,Liang Y,Bi J,Chen L,Zhang F,Cui Y,Jiang J.REGγregulates ERαdegradation via ubiquitin-proteasome pathway in breast cancer.Biochem Biophys Res Commun 2015;456:534-540[PMID:25490392 DOI:10.1016/j.bbrc.2014.11.124]
70 Liu H,Qiu J,Li N,Chen T,Cao X.Human phosphatidylethanolamine-binding protein 4 promotes transactivation of estrogen receptor alpha(ERalpha)in human cancer cells by inhibiting proteasome-dependent ERalpha degradation via association with Src.J Biol Chem 2010;285:21934-21942[PMID:20460377 DOI:10.1074/jbc.M110.109876]
71 Kim SH,Kang HJ,Na H,Lee MO.Trichostatin A enhances acetylation as well as protein stability of ERalpha through induction of p300 protein.Breast Cancer Res 2010;12:R22[PMID:20388208DOI:10.1186/bcr2562]
72 La Rosa P,Pesiri V,Leclercq G,Marino M,Acconcia F.Palmitoylation regulates 17β-estradiol-induced estrogen receptor-αdegradation and transcriptional activity.Mol Endocrinol 2012;26:762-774[PMID:22446104 DOI:10.1210/me.2011-1208]
73 Murphy LC,Seekallu SV,Watson PH.Clinical significance of estrogen receptor phosphorylation.Endocr Relat Cancer 2011;18:R1-14[PMID:21149515 DOI:10.1677/ERC-10-0070]
74 Thomas C,Gustafsson J?.Estrogen receptor mutations and functional consequences for breast cancer.Trends Endocrinol Metab 2015;26:467-476[PMID:26183887 DOI:10.1016/j.tem.2015.06.007]
75 Yeh WL,Shioda K,Coser KR,Rivizzigno D,Mc Sweeney KR,Shioda T.Fulvestrant-induced cell death and proteasomal degradation of estrogen receptorαprotein in MCF-7 cells require the CSK c-Src tyrosine kinase.PLo S One 2013;8:e60889[PMID:23593342 DOI:10.1371/journal.pone.0060889]
76 De Savi C,Bradbury RH,Rabow AA,Norman RA,Buttar D,Currie GS,Weir H,Donald C,Andrews D,Mac Faul P,Ballard P,Curwen J,Wilson Z,Richmond G,D’Cruz C,Powell S,Walker G,Hulse M,Tonge M.Abstract 3650:Discovery of the clinical candidate AZD9496:a potent and orally bioavailable selective estrogen receptor downregulator and antagonist.Cancer Research2015;75:3650[DOI:10.1158/1538-7445.AM2015-3650]
77 Lai A,Kahraman M,Govek S,Nagasawa J,Bonnefous C,Julien J,Douglas K,Sensintaffar J,Lu N,Lee KJ,Aparicio A,Kaufman J,Qian J,Shao G,Prudente R,Moon MJ,Joseph JD,Darimont B,Brigham D,Grillot K,Heyman R,Rix PJ,Hager JH,Smith ND.Identification of GDC-0810(ARN-810),an Orally Bioavailable Selective Estrogen Receptor Degrader(SERD)that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.J Med Chem 2015;58:4888-4904[PMID:25879485 DOI:10.1021/acs.jmedchem.5b00054]
78 Wardell SE,Nelson ER,Chao CA,Mc Donnell DP.Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen-resistant breast cancer:implications for treatment of advanced disease.Clin Cancer Res 2013;19:2420-2431[PMID:23536434DOI:10.1158/1078-0432.CCR-12-3771]
79 Garner F,Shomali M,Paquin D,Lyttle CR,Hattersley G.RAD1901:a novel,orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models.Anticancer Drugs 2015;26:948-956[PMID:26164151 DOI:10.1097/CAD.0000000000000271]
80 Kim JA,Kim MR,Kim O,Phuong NT,Yun J,Oh WK,Bae K,Kang KW.Amurensin G inhibits angiogenesis and tumor growth of tamoxifen-resistant breast cancer via Pin1 inhibition.Food Chem Toxicol 2012;50:3625-3634[PMID:22842120 DOI:10.1016/j.fct.2012.07.027]
81 Kim JH,Jung JH,Kim SH,Jeong SJ.Decursin exerts anti-cancer activity in MDA-MB-231 breast cancer cells via inhibition of the Pin1 activity and enhancement of the Pin1/p53 association.Phytother Res 2014;28:238-244[PMID:23580332 DOI:10.1002/ptr.4986]
82 Kotiyal S,Bhattacharya S.Breast cancer stem cells,EMT and therapeutic targets.Biochem Biophys Res Commun 2014;453:112-116[PMID:25261721 DOI:10.1016/j.bbrc.2014.09.069]
83 Li X,Li L,Zhou Q,Zhang N,Zhang S,Zhao R,Liu D,Jing Y,Zhao L.Synthesis of the novel elemonic acid derivatives as Pin1inhibitors.Bioorg Med Chem Lett 2014;24:5612-5615[PMID:25466185 DOI:10.1016/j.bmcl.2014.10.087]
84 Moore JD,Potter A.Pin1 inhibitors:Pitfalls,progress and cellular pharmacology.Bioorg Med Chem Lett 2013;23:4283-4291[PMID:23796453 DOI:10.1016/j.bmcl.2013.05.088]
85 Potter A,Oldfield V,Nunns C,Fromont C,Ray S,Northfield CJ,Bryant CJ,Scrace SF,Robinson D,Matossova N,Baker L,Dokurno P,Surgenor AE,Davis B,Richardson CM,Murray JB,Moore JD.Discovery of cell-active phenyl-imidazole Pin1inhibitors by structure-guided fragment evolution.Bioorg Med Chem Lett 2010;20:6483-6488[PMID:20932746 DOI:10.1016/j.bmcl.2010.09.063]
86 Wei S,Kozono S,Kats L,Nechama M,Li W,Guarnerio J,Luo M,You MH,Yao Y,Kondo A,Hu H,Bozkurt G,Moerke NJ,Cao S,Reschke M,Chen CH,Rego EM,Lo-Coco F,Cantley LC,Lee TH,Wu H,Zhang Y,Pandolfi PP,Zhou XZ,Lu KP.Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer.Nat Med 2015;21:457-466[PMID:25849135DOI:10.1038/nm.3839]
87 Xu GG,Slebodnick C,Etzkorn FA.Cyclohexyl ketone inhibitors of Pin1 dock in a trans-diaxial cyclohexane conformation.PLo SOne 2012;7:e44226[PMID:23028504 DOI:10.1371/journal.pone.0044226]
88 Stebbing J,Filipovic A,Ellis IO,Green AR,D’Silva TR,Lenz HJ,Coombes RC,Wang T,Lee SC,Giamas G.LMTK3 expression in breast cancer:association with tumor phenotype and clinical outcome.Breast Cancer Res Treat 2012;132:537-544[PMID:21671015 DOI:10.1007/s10549-011-1622-z]
89 Stebbing J,Filipovic A,Lit LC,Blighe K,Grothey A,Xu Y,Miki Y,Chow LW,Coombes RC,Sasano H,Shaw JA,Giamas G.LMTK3is implicated in endocrine resistance via multiple signaling pathways.Oncogene 2013;32:3371-3380[PMID:22869149 DOI:10.1038/onc.2012.343]
90 Zhao G,Guo J,Li D,Jia C,Yin W,Sun R,Lv Z,Cong X.Micro RNA-34a suppresses cell proliferation by targeting LMTK3in human breast cancer mcf-7 cell line.DNA Cell Biol 2013;32:699-707[PMID:24050776 DOI:10.1089/dna.2013.2130]
91 Jacobs KM,Bhave SR,Ferraro DJ,Jaboin JJ,Hallahan DE,Thotala D.GSK-3β:A Bifunctional Role in Cell Death Pathways.Int J Cell Biol 2012;2012:930710[PMID:22675363 DOI:10.1155/2012/930710]
92 Kim HM,Kim CS,Lee JH,Jang SJ,Hwang JJ,Ro S,Choi J.CG0009,a novel glycogen synthase kinase 3 inhibitor,induces cell death through cyclin D1 depletion in breast cancer cells.PLo SOne 2013;8:e60383[PMID:23565238 DOI:10.1371/journal.pone.0060383]
93 Mc Cubrey JA,Davis NM,Abrams SL,Montalto G,Cervello M,Basecke J,Libra M,Nicoletti F,Cocco L,Martelli AM,Steelman LS.Diverse roles of GSK-3:tumor promoter-tumor suppressor,target in cancer therapy.Adv Biol Regul 2014;54:176-196[PMID:24169510 DOI:10.1016/j.jbior.2013.09.013]
94 Mishra R.Glycogen synthase kinase 3 beta:can it be a target for oral cancer.Mol Cancer 2010;9:144[PMID:20537194 DOI:10.1186/1476-4598-9-144]
95 Ertel A,Dean JL,Rui H,Liu C,Witkiewicz AK,Knudsen KE,Knudsen ES.RB-pathway disruption in breast cancer:differential association with disease subtypes,disease-specific prognosis and therapeutic response.Cell Cycle 2010;9:4153-4163[PMID:20948315 DOI:10.4161/cc.9.20.13454]
96 Lehn S,Fern?M,Jirstr?m K,Rydén L,Landberg G.A non-functional retinoblastoma tumor suppressor(RB)pathway in premenopausal breast cancer is associated with resistance to tamoxifen.Cell Cycle2011;10:956-962[PMID:21358261 DOI:10.4161/cc.10.6.15074]
97 TreréD,Brighenti E,Donati G,Ceccarelli C,Santini D,Taffurelli M,Montanaro L,Derenzini M.High prevalence of retinoblastoma protein loss in triple-negative breast cancers and its association with a good prognosis in patients treated with adjuvant chemotherapy.Ann Oncol 2009;20:1818-1823[PMID:19556322 DOI:10.1093/annonc/mdp209]
98 Witkiewicz AK,Knudsen ES.Retinoblastoma tumor suppressor pathway in breast cancer:prognosis,precision medicine,and therapeutic interventions.Breast Cancer Res 2014;16:207[PMID:25223380 DOI:10.1186/bcr3652]
99 Alam M,Rajabi H,Ahmad R,Jin C,Kufe D.Targeting the MUC1-Concoprotein inhibits self-renewal capacity of breast cancer cells.Oncotarget 2014;5:2622-2634[PMID:24770886 DOI:10.18632/oncotarget.1848]
100 Kharbanda A,Rajabi H,Jin C,Raina D,Kufe D.Oncogenic MUC1-C promotes tamoxifen resistance in human breast cancer.Mol Cancer Res 2013;11:714-723[PMID:23538857 DOI:10.1158/1541-7786.MCR-12-0668]
101 Pitroda SP,Khodarev NN,Beckett MA,Kufe DW,Weichselbaum RR.MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment.Proc Natl Acad Sci USA 2009;106:5837-5841[PMID:19289846DOI:10.1073/pnas.0812029106]
102 Alam M,Bouillez A,Tagde A,Ahmad R,Rajabi H,Maeda T,Hiraki M,Suzuki Y,Kufe D.MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway.Mol Cancer Res 2016;14:1266-1276[PMID:27658423DOI:10.1158/1541-7786.MCR-16-0233]
103 Jin C,Rajabi H,Kufe D.mi R-1226 targets expression of the mucin 1 oncoprotein and induces cell death.Int J Oncol 2010;37:61-69[PMID:20514397]
104 Sachdeva M,Mo YY.Micro RNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1.Cancer Res 2010;70:378-387[PMID:19996288 DOI:10.1158/0008-5472.CAN-09-2021]
105 Lacunza E,Baudis M,Colussi AG,Segal-Eiras A,Croce MV,Abba MC.MUC1 oncogene amplification correlates with protein overexpression in invasive breast carcinoma cells.Cancer Genet Cytogenet 2010;201:102-110[PMID:20682394 DOI:10.1016/j.cancergencyto.2010.05.015]
106 Rajabi H,Jin C,Ahmad R,Mc Clary C,Joshi MD,Kufe D.MUCIN 1 ONCOPROTEIN EXPRESSION IS SUPPRESSED BYTHE mi R-125b ONCOMIR.Genes Cancer 2010;1:62-68[PMID:20729973 DOI:10.1177/1947601909357933]
107 Zhou Y,Rajabi H,Kufe D.Mucin 1 C-terminal subunit oncoprotein is a target for small-molecule inhibitors.Mol Pharmacol 2011;79:886-893[PMID:21346142 DOI:10.1124/mol.110.070797]
108 Yuan S,Shi C,Ling R,Wang T,Wang H,Han W.Immunization with two recombinant Bacillus Calmette-Guérin vaccines that combine the expression of multiple tandem repeats of mucin-1 and colony stimulating-factor suppress breast tumor growth in mice.JCancer Res Clin Oncol 2010;136:1359-1367[PMID:20127358DOI:10.1007/s00432-010-0787-x]
109 Yuan S,Shi C,Liu L,Han W.MUC1-based recombinant Bacillus Calmette-Guerin vaccines as candidates for breast cancer immuno-therapy.Expert Opin Biol Ther 2010;10:1037-1048[PMID:20420512DOI:10.1517/14712598.2010.485185]
110 Kotzsch M,Kirchner T,Soelch S,Sch?fer S,Friedrich K,Baretton G,Magdolen V,Luther T.Inverse association of rab31 and mucin-1(CA15-3)antigen levels in estrogen receptor-positive(ER+)breast cancer tissues with clinicopathological parameters and patients’prognosis.Am J Cancer Res 2017;7:1959-1970[PMID:28979817]
111 Fowler AM,Solodin N,Preisler-Mashek MT,Zhang P,Lee AV,Alarid ET.Increases in estrogen receptor-alpha concentration in breast cancer cells promote serine 118/104/106-independent AF-1transactivation and growth in the absence of estrogen.FASEB J2004;18:81-93[PMID:14718389 DOI:10.1096/fj.03-0038com]
112 Fowler AM,Solodin NM,Valley CC,Alarid ET.Altered target gene regulation controlled by estrogen receptor-alpha concentration.Mol Endocrinol 2006;20:291-301[PMID:16179380 DOI:10.1210/me.2005-0288]