CLC number: R737.9
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2019-04-17
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Marissa Leonard, Xiaoting Zhang. Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer[J]. Journal of Zhejiang University Science B, 2019, 20(5): 381-390.
@article{title="Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer",
author="Marissa Leonard, Xiaoting Zhang",
journal="Journal of Zhejiang University Science B",
volume="20",
number="5",
pages="381-390",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900163"
}
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%T Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer
%A Marissa Leonard
%A Xiaoting Zhang
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%P 381-390
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900163
TY - JOUR
T1 - Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer
A1 - Marissa Leonard
A1 - Xiaoting Zhang
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 5
SP - 381
EP - 390
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900163
Abstract: breast cancer, one of the most frequent cancer types, is a leading cause of death in women worldwide. estrogen receptor (ER) α is a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer. About 75% of breast cancer cases are diagnosed as ER-positive; however, nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies. Recent studies have identified an ER coactivator, mediator Subunit 1 (MED1)%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>mediator Subunit 1 (MED1), as a unique, tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance. MED1 is overexpressed in over 50% of human breast cancer cases and co-amplifies with another important breast cancer gene, receptor tyrosine kinase HER2. Clinically, MED1 expression highly correlates with poor disease-free survival of breast cancer patients, and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment. In this review, we discuss the biochemical characterization of MED1 and its associated MED1/mediator complex, its crosstalk with HER2 in anti-estrogen resistance, breast cancer stem cell formation, and metastasis both in vitro and in vivo. Furthermore, we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.
[1]Abderrahman B, Jordan VC, 2019a. The first targeted therapy to treat cancer: the tamoxifen tale. In: Zhang XT (Ed.), Estrogen Receptor and Breast Cancer. Humana Press, Cham, p.151-188.
[2]Abderrahman B, Jordan VC, 2019b. A novel strategy to improve women’s health: selective estrogen receptor modulators. In: Zhang XT (Ed.), Estrogen Receptor and Breast Cancer. Humana Press, Cham, p.189-213.
[3]Acevedo ML, Lee KC, Stender JD, et al., 2004. Selective recognition of distinct classes of coactivators by a ligand-inducible activation domain. Mol Cell, 13(5):725-738.
[4]Bick G, Zhao D, Zhang XT, 2019. Estrogen receptor-mediated gene transcription and cistrome. In: Zhang XT (Ed.), Estrogen Receptor and Breast Cancer. Humana Press, Cham, p.49-70.
[5]Blazek E, Mittler G, Meisterernst M, 2005. The Mediator of RNA polymerase II. Chromosoma, 113(8):399-408.
[6]Boube M, Joulia L, Cribbs DL, et al., 2002. Evidence for a Mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. Cell, 110(2):143-151.
[7]Cui JJ, Germer K, Wu TY, et al., 2012. Cross-talk between HER2 and MED1 regulates tamoxifen resistance of human breast cancer cells. Cancer Res, 72(21):5625-5634.
[8]Dutertre M, Smith CL, 2000. Molecular mechanisms of selective estrogen receptor modulator (SERM) action. J Pharmacol Exp Ther, 295(2):431-437.
[9]Eastell R, Adams JE, Coleman RE, et al., 2008. Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol, 26(7):1051-1058.
[10]Ferlay J, Soerjomataram I, Dikshit R, et al., 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 136(5):E359-E386.
[11]Fondell JD, Ge H, Roeder RG, 1996. Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc Natl Acad Sci USA, 93(16):8329-8333.
[12]Fu XY, de Angelis C, Veeraraghavan J, et al., 2019. Molecular mechanisms of endocrine resistance. In: Zhang XT (Ed.), Estrogen Receptor and Breast Cancer. Humana Press, Cham, p.265-307.
[13]Germer K, Pi FM, Guo PX, et al., 2013. Conjugation of RNA aptamer to RNA nanoparticles for targeted drug delivery. In: Guo PX, Haque F (Eds.), RNA Nanotechnology and Therapeutics. CRC Press, Boca Raton, Florida, p.399-408.
[14]Glass CK, Rosenfeld MG, 2000. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev, 14(2):121-141.
[15]Guo PX, 2010. The emerging field of RNA nanotechnology. Nat Nanotechnol, 5(12):833-842.
[16]Hall JM, McDonnell DP, 2005. Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting. Mol Interv, 5(6):343-357.
[17]Heery DM, Kalkhoven E, Hoare S, et al., 1997. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature, 387(6634):733-736.
[18]Holmes KA, Hurtado A, Brown GD, et al., 2012. Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells. Proc Natl Acad Sci USA, 109(8):2748-2753.
[19]Hurtado A, Holmes KA, Ross-Innes CS, et al., 2011. FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat Genet, 43(1):27-33.
[20]Jasinski D, Haque F, Binzel DW, et al., 2017. Advancement of the emerging field of RNA nanotechnology. ACS Nano, 11(2):1142-1164.
[21]Jensen EV, Jordan VC, 2003. The estrogen receptor: a model for molecular medicine. Clin Cancer Res, 9(6):1980-1989.
[22]Jiang PP, Hu QP, Ito M, et al., 2010. Key roles for MED1 LxxLL motifs in pubertal mammary gland development and luminal-cell differentiation. Proc Natl Acad Sci USA, 107(15):6765-6770.
[23]Kang YK, Guermah M, Yuan CX, et al., 2002. The TRAP/ Mediator coactivator complex interacts directly with estrogen receptors α and β through the TRAP220 subunit and directly enhances estrogen receptor function in vitro. Proc Natl Acad Sci USA, 99(5):2642-2647.
[24]Kedar R, Bourne TH, Collins WP, et al., 1994. Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial. Lancet, 343(8909):1318-1321.
[25]Kumar V, Green S, Stack G, et al., 1987. Functional domains of the human estrogen receptor. Cell, 51(6):941-951.
[26]Leonard M, Tan J, Yang YG, et al., 2019. Emerging therapeutic approaches to overcome breast cancer endocrine resistance. In: Zhang XT (Ed.), Estrogen Receptor and Breast Cancer. Humana Press, Cham, p.379-403.
[27]Luoh SW, 2002. Amplification and expression of genes from the 17q11~q12 amplicon in breast cancer cells. Cancer Genet Cytogenet, 136(1):43-47.
[28]Lupien M, Meyer CA, Bailey ST, et al., 2010. Growth factor stimulation induces a distinct ERα cistrome underlying breast cancer endocrine resistance. Genes Dev, 24(19):2219-2227.
[29]Magnani L, Ballantyne EB, Zhang XY, et al., 2011. PBX1 genomic pioneer function drives ERα signaling underlying progression in breast cancer. PLoS Genet, 7(11):e1002368.
[30]Malik S, Roeder RG, 2005. Dynamic regulation of pol II transcription by the mammalian Mediator complex. Trends Biochem Sci, 30(5):256-263.
[31]Mangelsdorf DJ, Thummel C, Beato M, et al., 1995. The nuclear receptor superfamily: the second decade. Cell, 83(6):835-839.
[32]McDonnell DP, Wardell SE, 2010. The molecular mechanisms underlying the pharmacological actions of ER modulators: implications for new drug discovery in breast cancer. Curr Opin Pharmacol, 10(6):620-628.
[33]McKenna NJ, O'Malley BW, 2002. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell, 108(4):465-474.
[34]Mourits MJE, de Vries EGE, Willemse PHB, et al., 2001. Tamoxifen treatment and gynecologic side effects: a review. Obstet Gynecol, 97(5):855-866.
[35]Murtaza M, Dawson SJ, Tsui DWY, et al., 2013. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature, 497(7447):108-112.
[36]Myers LC, Kornberg RD, 2000. Mediator of transcriptional regulation. Ann Rev Biochem, 69:729-749.
[37]Nagalingam A, Tighiouart M, Ryden L, et al., 2012. Med1 plays a critical role in the development of tamoxifen resistance. Carcinogenesis, 33(4):918-930.
[38]Pandey PK, Udayakumar TS, Lin XJ, et al., 2005. Activation of TRAP/Mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation. Mol Cell Biol, 25(24):10695-10710.
[39]Parker JS, Mullins M, Cheang MCU, et al., 2009. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol, 27(8):1160-1167.
[40]Perou CM, Sørlie T, Eisen MB, et al., 2000. Molecular portraits of human breast tumours. Nature, 406(6797):747-752.
[41]Plevin MJ, Mills MM, Ikura M, 2005. The LxxLL motif: a multifunctional binding sequence in transcriptional regulation. Trends Biochem Sci, 30(2):66-69.
[42]Reinert T, Matsunuma R, Han AR, et al., 2019. Endocrine therapy in clinical practice. In: Zhang XT (Ed.), Estrogen Receptor and Breast Cancer. Humana Press, Cham, p.215-240.
[43]Roeder RG, 1998. Role of general and gene-specific cofactors in the regulation of eukaryotic transcription. Cold Spring Harb Symp Quant Biol, 63:201-218.
[44]Roeder RG, 2003. The eukaryotic transcriptional machinery: complexities and mechanisms unforeseen. Nat Med, 9(10):1239-1244.
[45]Ross-Innes CS, Stark R, Teschendorff AE, et al., 2012. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature, 481(7381):389-393.
[46]Savkur RS, Burris TP, 2004. The coactivator LxxLL nuclear receptor recognition motif. J Pept Res, 63(3):207-212.
[47]Shang YF, Hu X, Direnzo J, et al., 2000. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell, 103(6):843-852.
[48]Shou J, Massarweh S, Osborne CK, et al., 2004. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst, 96(12):926-935.
[49]Shu D, Shu Y, Haque F, et al., 2011. Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nat Nanotechnol, 6(10):658-667.
[50]The Cancer Genome Atlas Network, 2012. Comprehensive molecular portraits of human breast tumours. Nature, 490(7418):61-70.
[51]Vasquez YM, Lee Kraus W, 2019. The estrogen-regulated transcriptome: rapid, robust, extensive, and transient. In: Zhang XT (Ed.), Estrogen Receptor and Breast Cancer. Humana Press, Cham, p.95-127.
[52]Wärnmark A, Almlöf T, Leers J, et al., 2001. Differential recruitment of the mammalian Mediator subunit TRAP220 by estrogen receptors ERα and ERβ. J Biol Chem, 276(26):23397-23404.
[53]Yang YG, Leonard M, Zhang YJ, et al., 2018. HER2-driven breast tumorigenesis relies upon interactions of the estrogen receptor with coactivator MED1. Cancer Res, 78(2):422-435.
[54]Zhang DX, Jiang PP, Xu QQ, et al., 2011. Arginine and glutamate-rich 1 (ARGLU1) interacts with Mediator subunit 1 (MED1) and is required for estrogen receptor-mediated gene transcription and breast cancer cell growth. J Biol Chem, 286(20):17746-17754.
[55]Zhang LJ, Cui JJ, Leonard M, et al., 2013. Silencing MED1 sensitizes breast cancer cells to pure anti-estrogen fulvestrant in vitro and in vivo. PLoS ONE, 8(7):e70641.
[56]Zhang XT, Krutchinsky A, Fukuda A, et al., 2005. MED1/ TRAP220 exists predominantly in a TRAP/Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol Cell, 19(1):89-100.
[57]Zhang YJ, Leonard M, Shu Y, et al., 2017. Overcoming tamoxifen resistance of human breast cancer by targeted gene silencing using multifunctional pRNA nanoparticles. ACS Nano, 11(1):335-346.
[58]Zhu YJ, Qi C, Jain S, et al., 1999. Amplification and overexpression of peroxisome proliferator-activated receptor binding protein (PBP/PPARBP) gene in breast cancer. Proc Natl Acad Sci USA, 96(19):10848-10853.
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