Luminal breast cancer identity is determined by loss of glucocorticoid receptor activity.
ZBTB16
breast cancer
glucocorticoids
luminal breast cancer subtypes
nuclear receptors
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 Dec 2023
07 Dec 2023
Historique:
revised:
27
09
2023
received:
21
03
2023
accepted:
04
10
2023
medline:
11
12
2023
pubmed:
30
10
2023
entrez:
30
10
2023
Statut:
ppublish
Résumé
Glucocorticoid receptor (GR) is a transcription factor that plays a crucial role in cancer biology. In this study, we utilized an in silico-designed GR activity signature to demonstrate that GR relates to the proliferative capacity of numerous primary cancer types. In breast cancer, the GR activity status determines luminal subtype identity and has implications for patient outcomes. We reveal that GR engages with estrogen receptor (ER), leading to redistribution of ER on the chromatin. Notably, GR activation leads to upregulation of the ZBTB16 gene, encoding for a transcriptional repressor, which controls growth in ER-positive breast cancer and associates with prognosis in luminal A patients. In relation to ZBTB16's repressive nature, GR activation leads to epigenetic remodeling and loss of histone acetylation at sites proximal to cancer-driving genes. Based on these findings, epigenetic inhibitors reduce viability of ER-positive breast cancer cells that display absence of GR activity. Our findings provide insights into how GR controls ER-positive breast cancer growth and may have implications for patients' prognostication and provide novel therapeutic candidates for breast cancer treatment.
Identifiants
pubmed: 37902007
doi: 10.15252/emmm.202317737
pmc: PMC10701603
doi:
Substances chimiques
Receptors, Glucocorticoid
0
Receptors, Estrogen
0
Banques de données
GEO
['GSE222799']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e17737Subventions
Organisme : KWF Kankerbestrijding (DCS)
ID : 12128
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)
ID : 91716401
Organisme : Oncode Institute
Informations de copyright
© 2023 Netherlands Cancer Institute. Published under the terms of the CC BY 4.0 license.
Références
EMBO Mol Med. 2023 Dec 7;15(12):e17737
pubmed: 37902007
Eur J Cancer. 2018 Oct;102:40-48
pubmed: 30125761
Cancer Res. 2011 Oct 15;71(20):6360-70
pubmed: 21868756
Nature. 2000 Aug 17;406(6797):747-52
pubmed: 10963602
J Clin Oncol. 2023 Oct 20;41(30):4790-4793
pubmed: 37535891
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Epigenetics. 2014 Jun;9(6):851-9
pubmed: 24622770
Cell Metab. 2011 Feb 2;13(2):170-82
pubmed: 21284984
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W551-4
pubmed: 16845068
Br J Cancer. 2004 Mar;90 Suppl 1:S2-6
pubmed: 15094757
Mol Cell. 2017 May 4;66(3):321-331.e6
pubmed: 28475868
Nucleic Acids Res. 2021 Apr 19;49(7):3856-3875
pubmed: 33751115
Curr Opin Genet Dev. 1998 Oct;8(5):532-8
pubmed: 9794823
Bioinformatics. 2010 Jun 15;26(12):i237-45
pubmed: 20529912
Int J Mol Sci. 2021 May 31;22(11):
pubmed: 34073101
Methods Mol Biol. 2016;1355:251-60
pubmed: 26584931
Ann Transl Med. 2021 Apr;9(8):707
pubmed: 33987405
Endocr Rev. 2014 Aug;35(4):671-93
pubmed: 24937701
Nucleic Acids Res. 2019 Jul 2;47(W1):W206-W211
pubmed: 31053864
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7602-7
pubmed: 27325774
J Allergy Clin Immunol. 2004 Jun;113(6):1100-8
pubmed: 15208591
J Clin Invest. 2017 Apr 3;127(4):1136-1145
pubmed: 28319043
Nat Methods. 2017 Nov;14(11):1083-1086
pubmed: 28991892
J Clin Oncol. 2019 May 10;37(14):1169-1178
pubmed: 30807234
Nat Commun. 2021 Jul 16;12(1):4360
pubmed: 34272384
Curr Pharm Des. 2010;16(32):3593-600
pubmed: 20977423
J Clin Oncol. 2016 Mar 20;34(9):927-35
pubmed: 26786933
Nat Commun. 2018 Feb 2;9(1):482
pubmed: 29396493
JAMA Oncol. 2017 Nov 01;3(11):1503-1510
pubmed: 28662222
Cancer Res. 2019 Oct 15;79(20):5260-5271
pubmed: 31444154
N Engl J Med. 2017 Nov 9;377(19):1836-1846
pubmed: 29117498
Nat Methods. 2011 Jun 26;8(8):659-61
pubmed: 21706014
J Pathol. 2017 Feb;241(3):375-391
pubmed: 27861902
Clin Cancer Res. 2018 Jul 15;24(14):3433-3446
pubmed: 29636357
Breast Cancer Res. 2019 Jul 24;21(1):82
pubmed: 31340854
J Clin Oncol. 2009 Mar 10;27(8):1160-7
pubmed: 19204204
J Natl Cancer Inst. 2018 Jul 1;110(7):726-733
pubmed: 29361175
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Nat Cancer. 2022 Feb;3(2):232-250
pubmed: 35221336
Dev Cell. 2002 Oct;3(4):499-510
pubmed: 12408802
Histol Histopathol. 2008 Jan;23(1):77-85
pubmed: 17952860
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Cell Metab. 2022 Mar 1;34(3):473-486.e9
pubmed: 35120589
Appl Immunohistochem Mol Morphol. 2010 May;18(3):254-7
pubmed: 19875955
Cell Rep. 2013 Feb 21;3(2):342-9
pubmed: 23403292
Nat Genet. 2021 Sep;53(9):1334-1347
pubmed: 34493872
J Pathol. 2006 Jul;209(3):317-27
pubmed: 16639692
Bioinformatics. 2015 Sep 1;31(17):2761-9
pubmed: 25957351
Breast. 2015 Nov;24 Suppl 2:S26-35
pubmed: 26253814
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
pubmed: 11553815
Clin Epigenetics. 2020 Jun 9;12(1):82
pubmed: 32517789
Oncogene. 2001 Apr 30;20(19):2465-75
pubmed: 11402341
Nat Methods. 2020 Jan;17(1):41-44
pubmed: 31768060
Nat Commun. 2022 Jan 26;13(1):514
pubmed: 35082299
Blood Cancer J. 2017 Jun 30;7(6):e577
pubmed: 28665419
Mol Cell Proteomics. 2014 Sep;13(9):2513-26
pubmed: 24942700
Endocr Relat Cancer. 2021 May 11;28(6):R157-R171
pubmed: 33852423
Nat Med. 2021 Feb;27(2):310-320
pubmed: 33462444
Cancer Cell. 2016 Mar 14;29(3):407-422
pubmed: 26947176
FASEB J. 2013 Oct;27(10):4194-203
pubmed: 23804241
Cell. 2013 Dec 5;155(6):1309-22
pubmed: 24315100
Anticancer Res. 2005 May-Jun;25(3c):2453-60
pubmed: 16080475
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
Nature. 2019 Mar;567(7749):540-544
pubmed: 30867597
Mol Endocrinol. 2005 Feb;19(2):340-9
pubmed: 15471946
JAMA Oncol. 2019 Sep 01;5(9):1304-1309
pubmed: 31393518
Mol Aspects Med. 2021 Apr;78:100939
pubmed: 33358533
J Med Internet Res. 2021 Jul 26;23(7):e27633
pubmed: 34309564
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925