Estrogen Receptor Alpha and its Ubiquitination in Breast Cancer Cells

Page: [690 - 704] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

More than 70% of all breast cancer cases are estrogen receptor alpha-positive (ERα). ERα is a member of the nuclear receptor family, and its activity is implicated in the gene transcription linked to the proliferation of breast cancer cells, as well as in extranuclear signaling pathways related to the development of resistance to endocrine therapy. Protein-protein interactions and posttranslational modifications of ERα underlie critical mechanisms that modulate its activity. In this review, the relationship between ERα and ubiquitin protein (Ub), was investigated in the context of breast cancer cells. Interestingly, Ub can bind covalently or non-covalently to ERα resulting in either a proteolytic or non-proteolytic fate for this receptor. Thereby, Ub-dependent molecular pathways that modulate ERα signaling may play a central role in breast cancer progression, and consequently, present critical targets for treatment of this disease.

Keywords: Estrogen receptor alpha, breast cancer, monoubiquitination, polyubiquitination, non-covalent ubiquitin binding, endocrine therapy.

Graphical Abstract

[1]
Chen T, Zhang N, Moran MS, et al. Borderline er-positive primary breast cancer gains no significant survival benefit from endocrine therapy: A systematic review and meta-analysis. Clinical Breast Cancer 2018; 18: 1-8.
[2]
Collins LC, Botero ML, Schnitt SJ. Bimodal frequency distribution of estrogen receptor immunohistochemical staining results in breast cancer: an analysis of 825 cases. Am J Clin Pathol 2005; 123: 16-20.
[3]
Curigliano G, Burstein HJ. E PW, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol 2017; 28: 1700-2.
[4]
Hammond ME, Hayes DF, Dowsett M, et al. American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 2010; 28: 2784-95.
[5]
Yi M, Huo L, Koenig KB, et al. Which threshold for ER positivity? a retrospective study based on 9639 patients. Ann Oncol 2014; 25: 1004-11.
[6]
Kumar R, Zakharov MN, Khan SH, et al. The dynamic structure of the estrogen receptor. J Amino Acids 2011; 2011: 812540.
[7]
Mader S, Chambon P, White JH. Defining a minimal estrogen receptor DNA binding domain. Nucleic Acids Res 1993; 21: 1125-32.
[8]
Nardulli AM, Greene GL, Shapiro DJ. Human estrogen receptor bound to an estrogen response element bends DNA. Mol Endocrinol 1993; 7: 331-40.
[9]
Billon-Gales A, Krust A, Fontaine C, et al. Activation function 2 (AF2) of estrogen receptor-alpha is required for the atheroprotective action of estradiol but not to accelerate endothelial healing. Proc Natl Acad Sci USA 2011; 108: 13311-6.
[10]
Metivier R, Penot G, Flouriot G, Pakdel F. Synergism between ERalpha transactivation function 1 (AF-1) and AF-2 mediated by steroid receptor coactivator protein-1: requirement for the AF-1 alpha-helical core and for a direct interaction between the N- and C-terminal domains. Mol Endocrinol 2001; 15: 1953-70.
[11]
Smirnova NF, Fontaine C, Buscato M, et al. The Activation function-1 of estrogen receptor alpha prevents arterial neointima development through a direct effect on smooth muscle cells. Circ Res 2015; 117: 770-8.
[12]
Vrtacnik P, Ostanek B, Mencej-Bedrac S, Marc J. The many faces of estrogen signaling. Biochem Med (Zagreb) 2014; 24: 329-42.
[13]
Zwart W, de Leeuw R, Rondaij M, et al. The hinge region of the human estrogen receptor determines functional synergy between AF-1 and AF-2 in the quantitative response to estradiol and tamoxifen. Journal of cell science 2010; 123: 1253-61.
[14]
Acconcia F, Ascenzi P, Fabozzi G, et al. S-palmitoylation modulates human estrogen receptor-alpha functions. Biochem Biophys Res Commun 2004; 316: 878-83.
[15]
Pedram A, Razandi M, Deschenes RJ, Levin ER. DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Molecular biology of the cell 2012; 23: 188-99.
[16]
Acconcia F, Kumar R. Signaling regulation of genomic and nongenomic functions of estrogen receptors. Cancer Lett 2006; 238: 1-14.
[17]
Caligiuri I, Toffoli G, Giordano A, Rizzolio F. pRb controls estrogen receptor alpha protein stability and activity. Oncotarget 2013; 4: 875-83.
[18]
Frei A, MacDonald G, Lund I, et al. Memo interacts with c-Src to control Estrogen Receptor alpha sub-cellular localization. Oncotarget 2016; 7: 56170-82.
[19]
Kumar R, Wang RA, Mazumdar A, et al. A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm. Nature 2002; 418: 654-7.
[20]
Vadlamudi RK, Balasenthil S, Sahin AA, et al. Novel estrogen receptor coactivator PELP1/MNAR gene and ERbeta expression in salivary duct adenocarcinoma: potential therapeutic targets. Hum Pathol 2005; 36: 670-5.
[21]
Bjornstrom L, Sjoberg M. Estrogen receptor-dependent activation of AP-1 via non-genomic signalling. Nuclear Receptor 2004; 2: 3.
[22]
Frasor J, Weaver A, Pradhan M, et al. Positive cross-talk between estrogen receptor and NF-kappaB in breast cancer. Cancer Res 2009; 69: 8918-25.
[23]
Kato S. Estrogen receptor-mediated cross-talk with growth factor signaling pathways. Breast Cancer 2001; 8: 3-9.
[24]
Lee AV, Cui X, Oesterreich S. Cross-talk among estrogen receptor, epidermal growth factor, and insulin-like growth factor signaling in breast cancer. Clin Cancer Res 2001; 7: 4429s-35s; discussion 11s- 12s..
[25]
Carroll JS, Liu XS, Brodsky AS, et al. Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell 2005; 122: 33-43.
[26]
Theodorou V, Stark R, Menon S, Carroll JS. GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility. Genome Res 2013; 23: 12-22.
[27]
Fleming FJ, Hill AD, McDermott EW, et al. Differential recruitment of coregulator proteins steroid receptor coactivator-1 and silencing mediator for retinoid and thyroid receptors to the estrogen receptor-estrogen response element by beta-estradiol and 4-hydroxytamoxifen in human breast cancer. J Clin Endocrinol Metab 2004; 89: 375-83.
[28]
Hah N, Kraus WL. Hormone-regulated transcriptomes: lessons learned from estrogen signaling pathways in breast cancer cells. Mol Cell Endocrinol 2014; 382: 652-64.
[29]
Hah N, Murakami S, Nagari A, et al. Enhancer transcripts mark active estrogen receptor binding sites. Genome Res 2013; 23: 1210-23.
[30]
Hervouet E, Cartron PF, Jouvenot M, Delage-Mourroux R. Epigenetic regulation of estrogen signaling in breast cancer. Epigenetics 2013; 8: 237-45.
[31]
Manavathi B, Samanthapudi VS, Gajulapalli VN. Estrogen receptor coregulators and pioneer factors: the orchestrators of mammary gland cell fate and development. Front Cell Dev Biol 2014; 2: 34.
[32]
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: 2013-27.
[33]
Tecalco-Cruz AC, Perez-Alvarado IA, Ramirez-Jarquin JO, Rocha-Zavaleta L. Nucleo-cytoplasmic transport of estrogen receptor alpha in breast cancer cells. Cell Signal 2017; 34: 121-32.
[34]
Tecalco-Cruz AC, Ramirez-Jarquin JO. Mechanisms that Increase Stability of Estrogen Receptor Alpha in Breast Cancer. Clinical breast cancer 2017; 17: 1-10.
[35]
Howell SJ, Johnston SR, Howell A. The use of selective estrogen receptor modulators and selective estrogen receptor down-regulators in breast cancer. Best practice & research Clinical endocrinology & metabolism 2004; 18: 47-66.
[36]
Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 2011; 62: 233-47.
[37]
Patel HK, Bihani T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment. Pharmacology & therapeutics 2018; 186: 1-24.
[38]
Osborne CK, Wakeling A, Nicholson RI. Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action. Br J Cancer 2004; 90(Suppl. 1): S2-6.
[39]
Wardell SE, Marks JR, McDonnell DP. The turnover of estrogen receptor alpha by the selective estrogen receptor degrader (SERD) fulvestrant is a saturable process that is not required for antagonist efficacy. Biochem Pharmacol 2011; 82: 122-30.
[40]
AlFakeeh A, Brezden-Masley C. Overcoming endocrine resistance in hormone receptor-positive breast cancer. Current oncology 2018; 25: S18-27.
[41]
Bernassola F, Karin M, Ciechanover A, Melino G. The HECT family of E3 ubiquitin ligases: multiple players in cancer development. Cancer Cell 2008; 14: 10-21.
[42]
Deshaies RJ, Joazeiro CA. RING domain E3 ubiquitin ligases. Annual review of biochemistry 2009; 78: 399-434.
[43]
Metzger MB, Pruneda JN, Klevit RE, Weissman AM. RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim Biophys Acta 2014; 1843: 47-60.
[44]
Morreale FE, Walden H. Types of Ubiquitin Ligases. Cell 2016; 165: 248-e1.
[45]
Scheffner M, Kumar S. Mammalian HECT ubiquitin-protein ligases: biological and pathophysiological aspects. Biochim Biophys Acta 2014; 1843: 61-74.
[46]
Zheng N, Shabek N. Ubiquitin Ligases: Structure, Function, and Regulation. Annu Rev Biochem 2017; 86: 129-57.
[47]
D’Arcy P, Wang X, Linder S. Deubiquitinase inhibition as a cancer therapeutic strategy. Pharmacol Ther 2015; 147: 32-54.
[48]
Helzer KT, Hooper C, Miyamoto S, Alarid ET. Ubiquitylation of nuclear receptors: new linkages and therapeutic implications. J Mol Endocrinol 2015; 54: R151-67.
[49]
Mevissen TET, Komander D. Mechanisms of Deubiquitinase Specificity and Regulation. Annual review of biochemistry 2017; 86: 159-92.
[50]
Sadowski M, Suryadinata R, Tan AR, et al. Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes. IUBMB Life 2012; 64: 136-42.
[51]
Bonacci T, Audebert S, Camoin L, et al. Regulation of nub1 activity through non-proteolytic mdm2-mediated ubiquitination. PLoS One 2017; 12: e0169988.
[52]
Fei C, Li Z, Li C, et al. Smurf1-mediated Lys29-linked nonproteolytic polyubiquitination of axin negatively regulates Wnt/beta-catenin signaling. Mol Cell Biol 2013; 33: 4095-105.
[53]
Hurley JH, Lee S, Prag G. Ubiquitin-binding domains. Biochem J 2006; 399: 361-72.
[54]
Kuslansky Y, Sominsky S, Jackman A, et al. Ubiquitin ligase E6AP mediates nonproteolytic polyubiquitylation of beta-catenin independent of the E6 oncoprotein. J Gen Virol 2016; 97: 3313-30.
[55]
Scott D, Oldham NJ, Strachan J, et al. Ubiquitin-binding domains: mechanisms of ubiquitin recognition and use as tools to investigate ubiquitin-modified proteomes. Proteomics 2015; 15: 844-61.
[56]
La Rosa P, Marino M, Acconcia F. 17beta-estradiol regulates estrogen receptor alpha monoubiquitination. IUBMB life 2011; 63: 49-53.
[57]
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: 5794-9.
[58]
La Rosa P, Acconcia F. Signaling functions of ubiquitin in the 17beta-estradiol (E2):estrogen receptor (ER) alpha network. J Steroid Biochem Mol Biol 2011; 127: 223-30.
[59]
Ma Y, Fan S, Hu C, et al. BRCA1 regulates acetylation and ubiquitination of estrogen receptor-alpha. Mol Endocrinol 2010; 24: 76-90.
[60]
La Rosa P, Pesiri V, Marino M, Acconcia F. 17beta-Estradiol-induced cell proliferation requires estrogen receptor (ER) alpha monoubiquitination. Cell Signal 2011; 23: 1128-35.
[61]
Wang S, Luo H, Wang C, et al. RNF8 identified as a co-activator of estrogen receptor alpha promotes cell growth in breast cancer. Biochim Biophys Acta 2017; 1863: 1615-28.
[62]
Zhu J, Zhao C, Kharman-Biz A, et al. The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor alpha and modulates estrogen-stimulated breast cancer cell proliferation. Oncogene 2014; 33: 4340-51.
[63]
Zhuang T, Yu S, Zhang L, et al. SHARPIN stabilizes estrogen receptor alpha and promotes breast cancer cell proliferation. Oncotarget 2017; 8: 77137-51.
[64]
Di Fiore PP, Polo S, Hofmann K. When ubiquitin meets ubiquitin receptors: a signalling connection. Nature reviews Molecular Cell Biol 2003; 4: 491-7.
[65]
Wang X, Terpstra EJ. Ubiquitin receptors and protein quality control. J Mol Cell Cardiol 2013; 55: 73-84.
[66]
Dikic I, Wakatsuki S, Walters KJ. Ubiquitin-binding domains - from structures to functions. Nature Rev Mol Cell Biol 2009; 10: 659-71.
[67]
Husnjak K, Dikic I. Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu Rev Biochem 2012; 81: 291-322.
[68]
Woelk T, Sigismund S, Penengo L, Polo S. The ubiquitination code: a signalling problem. Cell Div 2007; 2: 11.
[69]
Pesiri V, Di Muzio E, Polticelli F, Acconcia F. Selective binding of estrogen receptor alpha to ubiquitin chains. IUBMB Life 2016; 68: 569-77.
[70]
Pesiri V, La Rosa P, Stano P, Acconcia F. Identification of an estrogen receptor alpha non covalent ubiquitin-binding surface: role in 17beta-estradiol-induced transcriptional activity. J Cell Sci 2013; 126: 2577-82.
[71]
Bhatt S, Xiao Z, Meng Z, Katzenellenbogen BS. Phosphorylation by p38 mitogen-activated protein kinase promotes estrogen receptor alpha turnover and functional activity via the SCF(Skp2) proteasomal complex. Mol Cell Biol 2012; 32: 1928-43.
[72]
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: 2901-14.
[73]
Hashizume R, Fukuda M, Maeda I, et al. The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation. J Biol Chem 2001; 276: 14537-40.
[74]
Saji S, Okumura N, Eguchi H, et al. MDM2 enhances the function of estrogen receptor alpha in human breast cancer cells. Biochem Biophys Res Commun 2001; 281: 259-65.
[75]
Sun J, Zhou W, Kaliappan K, et al. ERalpha phosphorylation at Y537 by Src triggers E6-AP-ERalpha binding, ERalpha ubiquitylation, promoter occupancy, and target gene expression. Mol Endocrinol 2012; 26: 1567-77.
[76]
Alarid ET. Lives and times of nuclear receptors. Mol Endocrinol 2006; 20: 1972-81.
[77]
Alarid ET, Bakopoulos N, Solodin N. Proteasome-mediated proteolysis of estrogen receptor: a novel component in autologous down-regulation. Mol Endocrinol 1999; 13: 1522-34.
[78]
Nawaz Z, Lonard DM, Dennis AP, et al. Proteasome-dependent degradation of the human estrogen receptor. Proc Natl Acad Sci USA 1999; 96: 1858-62.
[79]
Lonard DM, Nawaz Z, Smith CL, O’Malley BW. The 26S proteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha transactivation. Mol Cell 2000; 5: 939-48.
[80]
Reid G, Hubner MR, Metivier R, et al. Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling. Mol Cell 2003; 11: 695-707.
[81]
Stenoien DL, Patel K, Mancini MG, et al. FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent. Nature cell biology 2001; 3: 15-23.
[82]
Metivier R, Reid G, Gannon F. Transcription in four dimensions: nuclear receptor-directed initiation of gene expression. EMBO Reports 2006; 7: 161-7.
[83]
Zhou W, Srinivasan S, Nawaz Z, Slingerland JM. ERalpha, SKP2 and E2F-1 form a feed forward loop driving late ERalpha targets and G1 cell cycle progression. Oncogene 2014; 33: 2341-53.
[84]
Henrich LM, Smith JA, Kitt D, et al. Extracellular signal-regulated kinase 7, a regulator of hormone-dependent estrogen receptor destruction. Mol Cell Biol 2003; 23: 5979-88.
[85]
Wang Y, Zong H, Chi Y, et al. Repression of estrogen receptor alpha by CDK11p58 through promoting its ubiquitin-proteasome degradation. J Biochem 2009; 145: 331-43.
[86]
Rajbhandari P, Schalper KA, Solodin NM, et al. Pin1 modulates ERalpha levels in breast cancer through inhibition of phosphorylation-dependent ubiquitination and degradation. Oncogene 2014; 33: 1438-47.
[87]
Tecalco-Cruz AC, Ramirez-Jarquin JO. Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer. World J Clin Oncol 2018; 9: 60-70.
[88]
Chai F, Liang Y, Bi J, et al. REGgamma regulates ERalpha degradation via ubiquitin-proteasome pathway in breast cancer. Biochem Biophys Res Commun 2015; 456: 534-40.
[89]
Liu H, Qiu J, Li N, et al. 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: 21934-42.
[90]
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: 1535-51.
[91]
Kim MY, Woo EM, Chong YT, et al. Acetylation of estrogen receptor alpha by p300 at lysines 266 and 268 enhances the deoxyribonucleic acid binding and transactivation activities of the receptor. Mol Endocrinol 2006; 20: 1479-93.
[92]
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.
[93]
Wang C, Fu M, Angeletti RH, et al. Direct acetylation of the estrogen receptor alpha hinge region by p300 regulates transactivation and hormone sensitivity. J Biol Chem 2001; 276: 18375-83.
[94]
Subramanian K, Jia D, Kapoor-Vazirani P, et al. Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol Cell 2008; 30: 336-47.
[95]
La Rosa P, Pesiri V, Leclercq G, et al. Palmitoylation regulates 17beta-estradiol-induced estrogen receptor-alpha degradation and transcriptional activity. Mol Endocrinol 2012; 26: 762-74.
[96]
Preisler-Mashek MT, Solodin N, Stark BL, et al. Ligand-specific regulation of proteasome-mediated proteolysis of estrogen receptor-alpha. Am J Physiol Endocrinol Metab 2002; 282: E891-8.
[97]
Valley CC, Solodin NM, Powers GL, et al. Temporal variation in estrogen receptor-alpha protein turnover in the presence of estrogen. J Mol Endocrinol 2008; 40: 23-34.
[98]
Fowler AM, Solodin N, Preisler-Mashek MT, et al. Increases in estrogen receptor-alpha concentration in breast cancer cells promote serine 118/104/106-independent AF-1 transactivation and growth in the absence of estrogen. FASEB 2004; 18: 81-93.
[99]
Fowler AM, Solodin NM, Valley CC, Alarid ET. Altered target gene regulation controlled by estrogen receptor-alpha concentration. Mol Endocrinol 2006; 20: 291-301.
[100]
Musgrove EA. Estrogen receptor degradation: a CUE for endocrine resistance? Breast Cancer Res 2011; 13: 312.
[101]
Pan X, Zhou T, Tai YH, et al. Elevated expression of CUEDC2 protein confers endocrine resistance in breast cancer. Nat Med 2011; 17: 708-14.
[102]
Lehn S, Ferno M, Jirstrom K, et al. A non-functional retinoblastoma tumor suppressor (RB) pathway in premenopausal breast cancer is associated with resistance to tamoxifen. Cell Cycle 2011; 10: 956-62.
[103]
Trere D, Brighenti E, Donati G, et al. 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: 1818-23.
[104]
Jin C, Rajabi H, Pitroda S, et al. Cooperative interaction between the MUC1-C oncoprotein and the Rab31 GTPase in estrogen receptor-positive breast cancer cells. PLoS One 2012; 7: e39432.
[105]
Giamas G, Filipovic A, Jacob J, et al. Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer. Nat Med 2011; 17: 715-9.
[106]
Stebbing J, Filipovic A, Ellis IO, et al. LMTK3 expression in breast cancer: association with tumor phenotype and clinical outcome. Breast Cancer Res Treat 2012; 132: 537-44.
[107]
Stebbing J, Filipovic A, Lit LC, et al. LMTK3 is implicated in endocrine resistance via multiple signaling pathways. Oncogene 2013; 32: 3371-80.
[108]
He X, Zheng Z, Song T, et al. c-Abl regulates estrogen receptor alpha transcription activity through its stabilization by phosphorylation. Oncogene 2010; 29: 2238-51.
[109]
Kim JA, Kim MR, Kim O, et al. Amurensin G inhibits angiogenesis and tumor growth of tamoxifen-resistant breast cancer via Pin1 inhibition. Food Chem Toxicol 2012; 50: 3625-34.
[110]
Long X, Nephew KP. Fulvestrant (ICI 182,780)-dependent interacting proteins mediate immobilization and degradation of estrogen receptor-alpha. J Biol Chem 2006; 281: 9607-15.
[111]
Yeh WL, Shioda K, Coser KR, et al. Fulvestrant-induced cell death and proteasomal degradation of estrogen receptor alpha protein in MCF-7 cells require the CSK c-Src tyrosine kinase. PLoS One 2013; 8: e60889.
[112]
De Savi C, Bradbury RH, Rabow AA, et al. Abstract 3650: Discovery of the clinical candidate AZD9496: a potent and orally bioavailable selective estrogen receptor downregulator and antagonist. Cancer Res 2015; 75: 3650.
[113]
Wardell SE, Nelson ER, Chao CA, McDonnell DP. Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen-resistant breast cancer: implications for treatment of advanced disease. Clin Cancer Res 2013; 19: 2420-31.
[114]
Garner F, Shomali M, Paquin D, et al. RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. Anticancer Drugs 2015; 26: 948-56.
[115]
Lai A, Kahraman M, Govek S, et al. 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: 4888-904.
[116]
Guo S, Zhang C, Bratton M, et al. ZB716, a steroidal selective estrogen receptor degrader (SERD), is orally efficacious in blocking tumor growth in mouse xenograft models. Oncotarget 2018; 9: 6924-37.
[117]
Tria GS, Abrams T, Baird J, et al. Discovery of LSZ102, a Potent, orally bioavailable selective estrogen receptor degrader (serd) for the treatment of estrogen receptor positive breast cancer. J Med Chem 2018; 61: 2837-64.
[118]
Deeks ED. Fulvestrant: a review in advanced breast cancer not previously treated with endocrine therapy. Drugs 2018; 78: 131-7.
[119]
Britschgi A, Duss S, Kim S, et al. The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERalpha. Nature 2017; 541: 541-5.
[120]
Angus L, Beije N, Jager A, et al. ESR1 mutations: Moving towards guiding treatment decision-making in metastatic breast cancer patients. Cancer Treatment Rev 2017; 52: 33-40.
[121]
Toy W, Weir H, Razavi P, et al. Activating ESR1 mutations differentially affect the efficacy of er antagonists. Cancer Discov 2017; 7: 277-87.
[122]
Reinert T, Goncalves R, Bines J. Implications of ESR1 mutations in hormone receptor-positive breast cancer. Curr Treatment Options Oncol 2018; 19: 24.
[123]
Bahreini A, Li Z, Wang P, et al. Mutation site and context dependent effects of ESR1 mutation in genome-edited breast cancer cell models. Breast Cancer Res 2017; 19: 60.
[124]
Jeselsohn R, Bergholz JS, Pun M, et al. Allele-specific chromatin recruitment and therapeutic vulnerabilities of ESR1 activating mutations. Cancer Cell 2018; 33: 173-86. e5
[125]
Harrod A, Fulton J, Nguyen VTM, et al. Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer. Oncogene 2017; 36: 2286-96.
[126]
Martin LA, Ribas R, Simigdala N, et al. Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance. Nat Commun 2017; 8: 1865.
[127]
Chu I, Arnaout A, Loiseau S, et al. Src promotes estrogen-dependent estrogen receptor alpha proteolysis in human breast cancer. J Clin Invest 2007; 117: 2205-15.
[128]
Fuqua SA, Wiltschke C, Zhang QX, et al. A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions. Cancer Res 2000; 60: 4026-9.
[129]
Herynk MH, Parra I, Cui Y, et al. Association between the estrogen receptor alpha A908G mutation and outcomes in invasive breast cancer. Clin Cancer Res 2007; 13: 3235-43.
[130]
Holst F, Singer CF. ESR1-amplification-associated estrogen receptor alpha activity in breast cancer. Trends Endocrinol Metab 2016; 27: 751-2.
[131]
Laenkholm AV, Knoop A, Ejlertsen B, et al. ESR1 gene status correlates with estrogen receptor protein levels measured by ligand binding assay and immunohistochemistry. Mol Oncol 2012; 6: 428-36.
[132]
Nielsen KV, Ejlertsen B, Muller S, et al. Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal patients with hormone receptor positive breast cancer. Breast Cancer Res Treat 2011; 127: 345-55.
[133]
Glidewell-Kenney C, Weiss J, Lee EJ, et al. ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol 2005; 245: 53-9.
[134]
Lin CY, Strom A, Vega VB, et al. Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells. Genome Biol 2004; 5: R66.
[135]
Ross-Innes CS, Stark R, Teschendorff AE, et al. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature 2012; 481: 389-93.
[136]
Cruz-Ramos E, Sandoval-Hernandez A, Tecalco-Cruz AC. Differential expression and molecular interactions of chromosome region maintenance 1 and calreticulin exportins in breast cancer cells. J Steroid Biochem Mol Biol 2019; 185: 7-16.
[137]
Chen C, Zhou Z, Ross JS, et al. The amplified WWP1 gene is a potential molecular target in breast cancer. Int J Cancer 2007; 121: 80-7.
[138]
Chen C, Zhou Z, Sheehan CE, et al. Overexpression of WWP1 is associated with the estrogen receptor and insulin-like growth factor receptor 1 in breast carcinoma. Int J Cancer 2009; 124: 2829-36.
[139]
Karunarathna U, Kongsema M, Zona S, et al. OTUB1 inhibits the ubiquitination and degradation of FOXM1 in breast cancer and epirubicin resistance. Oncogene 2016; 35: 1433-44.
[140]
Liu X, Sun L, Gursel DB, et al. The non-canonical ubiquitin activating enzyme UBA6 suppresses epithelial-mesenchymal transition of mammary epithelial cells. Oncotarget 2017; 8: 87480-93.
[141]
Stanisic V, Malovannaya A, Qin J, et al. OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity. J Biol Chem 2009; 284: 16135-45.
[142]
Tedesco D, Zhang J, Trinh L, et al. The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition. Neoplasia 2007; 9: 601-13.
[143]
Gajulapalli VNR, Malisetty VL, Chitta SK, Manavathi B. Oestrogen receptor negativity in breast cancer: a cause or consequence? Biosci Reports 2016; 36.
[144]
Puyang X, Furman C, Zheng GZ, et al. Discovery of selective estrogen receptor covalent antagonists for the treatment of eralpha(wt) and eralpha(mut) breast cancer. Cancer Discov 2018; 8: 1176-93.
[145]
Jiang Y, Deng Q, Zhao H, et al. Development of stabilized peptide-based protacs against estrogen receptor alpha. ACS Chem Biol 2018; 13: 628-35.
[146]
Tecalco Cruz AC, Mejia-Barreto K. Cell type-dependent regulation of free ISG15 levels and ISGylation. J Cell Commun Signaling 2017; 11: 127-35.
[147]
Tecalco-Cruz AC, Cruz-Ramos E. Protein ISGylation and free ISG15 levels are increased by interferon gamma in breast cancer cells. Biochem Biophys Res Commun 2018; 499: 973-8.
[148]
Wu F, Mo YY. Ubiquitin-like protein modifications in prostate and breast cancer. Frontiers in bioscience. J Virtual Lib 2007; 12: 700-11.
[149]
Wei X, Xu H, Kufe D. MUC1 oncoprotein stabilizes and activates estrogen receptor alpha. Mol Cell 2006; 21: 295-305.
[150]
Grisouard J, Medunjanin S, Hermani A, et al. 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: 2427-39.
[151]
Yang H, Yu N, Xu J, et al. SMURF1 facilitates estrogen receptor a signaling in breast cancer cells. J Exp Clin Cancer Res 2018; 37: 24.