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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

An Insight into the Role of E2F1 in Breast Cancer Progression, Drug Resistance, and Metastasis

Author(s): Zafar Abbas Shah, Faisal Nouroz, Samina Ejaz* and Asima Tayyeb

Volume 23, Issue 4, 2023

Published on: 01 August, 2022

Page: [365 - 376] Pages: 12

DOI: 10.2174/1566524022666220308095834

Price: $65

Abstract

Aims: This study aimed to investigate the role of E2F1 in breast cancer biology.

Background: Expression of E2F1, a transcription factor of many oncogenes and tumor suppressor genes, is lowered in several malignancies, including breast carcinoma.

Objectives: In the present study, we analyzed the status of E2F1 expression in association with diverse attributes of breast malignancy and its impact on cancer progression.

Methods: For this purpose, we used various freely available online applications for gene enrichment, expression, and methylation analysis to extract mutation-based E2F1 map, to measure E2F1 drug sensitivity, and to determine E2F1 association with DNA damage response proteins.

Results: Results revealed tissue-specific regulatory behavior of E2F1. Moreover, the key role of E2F1 in the promotion of metastasis, stem cell-mediated carcinogenesis, estrogen-mediated cell proliferation, and cellular defense system, has therefore highlighted it as a metaplastic marker and hot member of key resistome pathways.

Conclusion: The information thus generated can be employed for future implications in devising rational therapeutic strategies. Moreover, this study has provided a more detailed insight into the diagnostic and prognostic potential of E2F1.

Keywords: Breast Invasive Carcinoma (BRIC), Triple Negative Breast Carcinoma (TNBC), cellular proliferation, estrogen pathways, cyclin-dependent kinases (CDKs), biomarker.

« Previous
[1]
Denechaud PD, Fajas L, Giralt A. E2F1, a novel regulator of metabolism. Front Endocrinol (Lausanne) 2017; 8(8): 311.
[http://dx.doi.org/10.3389/fendo.2017.00311] [PMID: 29176962]
[2]
Black EP, Hallstrom T, Dressman HK, West M, Nevins JR. Distinctions in the specificity of E2F function revealed by gene expression signatures. Proc Natl Acad Sci USA 2005; 102(44): 15948-53.
[http://dx.doi.org/10.1073/pnas.0504300102] [PMID: 16249342]
[3]
Dyson NJ. RB1: a prototype tumor suppressor and an enigma. Genes Dev 2016; 30(13): 1492-502.
[http://dx.doi.org/10.1101/gad.282145.116] [PMID: 27401552]
[4]
Frolov MV, Dyson NJ. Molecular mechanisms of E2F-dependent activation and pRB-mediated repression. J Cell Sci 2004; 117(Pt 11): 2173-81.
[http://dx.doi.org/10.1242/jcs.01227] [PMID: 15126619]
[5]
Shats I, Deng M, Davidovich A, et al. Expression level is a key determinant of E2F1-mediated cell fate. Cell Death Differ 2017; 24(4): 626-37.
[http://dx.doi.org/10.1038/cdd.2017.12] [PMID: 28211871]
[6]
Polager S, Kalma Y, Berkovich E, Ginsberg D. E2Fs up-regulate expression of genes involved in DNA replication, DNA repair and mitosis. Oncogene 2002; 21(3): 437-46.
[http://dx.doi.org/10.1038/sj.onc.1205102] [PMID: 11821956]
[7]
Wu L, Timmers C, Maiti B, et al. The E2F1-3 transcription factors are essential for cellular proliferation. Nature 2001; 414(6862): 457-62.
[http://dx.doi.org/10.1038/35106593] [PMID: 11719808]
[8]
Stevens C, La Thangue NB. The emerging role of E2F-1 in the DNA damage response and checkpoint control. DNA Repair (Amst) 2004; 3(8-9): 1071-9.
[http://dx.doi.org/10.1016/j.dnarep.2004.03.034] [PMID: 15279795]
[9]
Fajas L, Landsberg RL, Huss-Garcia Y, Sardet C, Lees JA, Auwerx J. E2Fs regulate adipocyte differentiation. Dev Cell 2002; 3(1): 39-49.
[http://dx.doi.org/10.1016/S1534-5807(02)00190-9] [PMID: 12110166]
[10]
Liew CW, Boucher J, Cheong JK, et al. Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. Nat Med 2013; 19(2): 217-26.
[http://dx.doi.org/10.1038/nm.3056] [PMID: 23291629]
[11]
Tarangelo A, Lo N, Teng R, et al. Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression. Nat Commun 2015; 6(1): 10028.
[http://dx.doi.org/10.1038/ncomms10028] [PMID: 26639898]
[12]
Wu M, Seto E, Zhang J. E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells. Oncotarget 2015; 6(13): 11252-63.
[http://dx.doi.org/10.18632/oncotarget.3594] [PMID: 25816777]
[13]
Karamat U, Ejaz S. Overexpression of RAD50 is the Marker of Poor Prognosis and Drug Resistance in Breast Cancer Patients. Curr Cancer Drug Targets 2021; 21(2): 163-76.
[http://dx.doi.org/10.2174/1568009620666201009125507] [PMID: 33038913]
[14]
Li Z, Guo Y, Jiang H, et al. Differential regulation of MMPs by E2F1, Sp1 and NF-kappa B controls the small cell lung cancer invasive phenotype. BMC Cancer 2014; 14(1): 276.
[http://dx.doi.org/10.1186/1471-2407-14-276] [PMID: 24755270]
[15]
Ma X, Gao Y, Fan Y, et al. Overexpression of E2F1 promotes tumor malignancy and correlates with TNM stages in clear cell renal cell carcinoma. PLoS One 2013; 8(9): e73436.
[http://dx.doi.org/10.1371/journal.pone.0073436] [PMID: 24023875]
[16]
Engelmann D, Mayoli-Nüssle D, Mayrhofer C, et al. E2F1 promotes angiogenesis through the VEGF-C/VEGFR-3 axis in a feedback loop for cooperative induction of PDGF-B. J Mol Cell Biol 2013; 5(6): 391-403.
[http://dx.doi.org/10.1093/jmcb/mjt035] [PMID: 24014887]
[17]
Ren Z, Kang W, Wang L, et al. E2F1 renders prostate cancer cell resistant to ICAM-1 mediated antitumor immunity by NF-κB modulation. Mol Cancer 2014; 13(1): 84.
[http://dx.doi.org/10.1186/1476-4598-13-84] [PMID: 24742333]
[18]
Davis JN, Wojno KJ, Daignault S, et al. Elevated E2F1 inhibits transcription of the androgen receptor in metastatic hormone-resistant prostate cancer. Cancer Res 2006; 66(24): 11897-906.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-2497] [PMID: 17178887]
[19]
Zheng C, Ren Z, Wang H, et al. E2F1 Induces tumor cell survival via nuclear factor-kappaB-dependent induction of EGR1 transcription in prostate cancer cells. Cancer Res 2009; 69(6): 2324-31.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-4113] [PMID: 19276347]
[20]
Libertini SJ, Tepper CG, Guadalupe M, Lu Y, Asmuth DM, Mudryj M. E2F1 expression in LNCaP prostate cancer cells deregulates androgen dependent growth, suppresses differentiation, and enhances apoptosis. Prostate 2006; 66(1): 70-81.
[http://dx.doi.org/10.1002/pros.20314] [PMID: 16114066]
[21]
Wu L, de Bruin A, Wang H, et al. Selective roles of E2Fs for ErbB2- and Myc-mediated mammary tumorigenesis. Oncogene 2015; 34(1): 119-28.
[http://dx.doi.org/10.1038/onc.2013.511] [PMID: 24276244]
[22]
Vuaroqueaux V, Urban P, Labuhn M, et al. Low E2F1 transcript levels are a strong determinant of favorable breast cancer outcome. Breast Cancer Res 2007; 9(3): R33.
[http://dx.doi.org/10.1186/bcr1681] [PMID: 17535433]
[23]
Ho GH, Calvano JE, Bisogna M, Van Zee KJ. Expression of E2F-1 and E2F-4 is reduced in primary and metastatic breast carcinomas. Breast Cancer Res Treat 2001; 69(2): 115-22.
[http://dx.doi.org/10.1023/A:1012230115173] [PMID: 11759817]
[24]
DeGregori J, Johnson DG. Distinct and overlapping roles for E2F family members in transcription, proliferation and apoptosis. Curr Mol Med 2006; 6(7): 739-48.
[PMID: 17100600]
[25]
Baldini E, Camerini A, Sgambato A, et al. Cyclin A and E2F1 overexpression correlate with reduced disease-free survival in node-negative breast cancer patients. Anticancer Res 2006; 26(6B): 4415-21.
[PMID: 17201163]
[26]
Di Benedetto L, Giovanale V, Caserta D. Endometrial tubal metaplasia in a young puerperal woman after breast cancer. Int J Clin Exp Pathol 2015; 8(6): 7610-3.
[PMID: 26261678]
[27]
Schenone S, Brullo C, Musumeci F, Botta M. Novel dual Src/Abl inhibitors for hematologic and solid malignancies. Expert Opin Investig Drugs 2010; 19(8): 931-45.
[http://dx.doi.org/10.1517/13543784.2010.499898] [PMID: 20557276]
[28]
Sarker D, Ang JE, Baird R, et al. First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2015; 21(1): 77-86.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0947] [PMID: 25370471]
[29]
Berndt A, Miller S, Williams O, et al. The p110 δ structure: mechanisms for selectivity and potency of new PI(3)K inhibitors. Nat Chem Biol 2010; 6(2): 117-24.
[http://dx.doi.org/10.1038/nchembio.293] [PMID: 20081827]
[30]
Van Meter M, Simon M, Tombline G, et al. JNK phosphorylates SIRT6 to stimulate DNA double-strand break repair in response to oxidative stress by recruiting PARP1 to DNA breaks. Cell Rep 2016; 16(10): 2641-50.
[http://dx.doi.org/10.1016/j.celrep.2016.08.006] [PMID: 27568560]
[31]
Sellou H, Lebeaupin T, Chapuis C, et al. The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage. Mol Biol Cell 2016; 27(24): 3791-9.
[http://dx.doi.org/10.1091/mbc.E16-05-0269] [PMID: 27733626]
[32]
Haince JF, McDonald D, Rodrigue A, et al. PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites. J Biol Chem 2008; 283(2): 1197-208.
[http://dx.doi.org/10.1074/jbc.M706734200] [PMID: 18025084]
[33]
Araki K, Nakajima Y, Eto K, Ikeda MA. Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter. Oncogene 2003; 22(48): 7632-41.
[http://dx.doi.org/10.1038/sj.onc.1206840] [PMID: 14576826]
[34]
Caron MC, Sharma AK, O’Sullivan J, et al. Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks. Nat Commun 2019; 10(1): 2954.
[http://dx.doi.org/10.1038/s41467-019-10741-9] [PMID: 31273204]
[35]
Yao G, Lee TJ, Mori S, Nevins JR, You L. A bistable Rb-E2F switch underlies the restriction point. Nat Cell Biol 2008; 10(4): 476-82.
[http://dx.doi.org/10.1038/ncb1711] [PMID: 18364697]
[36]
Ren B, Cam H, Takahashi Y, et al. E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes Dev 2002; 16(2): 245-56.
[http://dx.doi.org/10.1101/gad.949802] [PMID: 11799067]
[37]
Coverley D, Laman H, Laskey RA. Distinct roles for cyclins E and A during DNA replication complex assembly and activation. Nat Cell Biol 2002; 4(7): 523-8.
[http://dx.doi.org/10.1038/ncb813] [PMID: 12080347]
[38]
Munro S, Oppermann U, La Thangue NB. Pleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancer. Oncogene 2014; 33(27): 3594-603.
[http://dx.doi.org/10.1038/onc.2013.316] [PMID: 23934193]
[39]
Polager S, Ofir M, Ginsberg D. E2F1 regulates autophagy and the transcription of autophagy genes. Oncogene 2008; 27(35): 4860-4.
[http://dx.doi.org/10.1038/onc.2008.117] [PMID: 18408756]
[40]
Rocca MS, Benna C, Goldin E, et al. E2F1 copy number variations in germline and breast cancer: a retrospective study of 222 Italian women. Mol Med 2021; 27(1): 26.
[http://dx.doi.org/10.1186/s10020-021-00287-2] [PMID: 33691613]

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