The G Protein-Coupled Estrogen Receptor (GPER) Expression Correlates with Pro-Metastatic Pathways in ER-Negative Breast Cancer: A Bioinformatics Analysis.
GPER
METABRIC
TCGA
bioinformatics
breast cancer
cell adhesion molecules
extracellular matrix
focal adhesion
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
04 03 2020
04 03 2020
Historique:
received:
05
02
2020
revised:
25
02
2020
accepted:
03
03
2020
entrez:
8
3
2020
pubmed:
8
3
2020
medline:
4
3
2021
Statut:
epublish
Résumé
The G protein-coupled estrogen receptor (GPER, formerly known as GPR30) is a seven-transmembrane receptor that mediates estrogen signals in both normal and malignant cells. In particular, GPER has been involved in the activation of diverse signaling pathways toward transcriptional and biological responses that characterize the progression of breast cancer (BC). In this context, a correlation between GPER expression and worse clinical-pathological features of BC has been suggested, although controversial data have also been reported. In order to better assess the biological significance of GPER in the aggressive estrogen receptor (ER)-negative BC, we performed a bioinformatics analysis using the information provided by The Invasive Breast Cancer Cohort of The Cancer Genome Atlas (TCGA) project and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets. Gene expression correlation and the statistical analysis were carried out with R studio base functions and the tidyverse package. Pathway enrichment analysis was evaluated with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the Database for Annotation, Visualization and Integrated Discovery (DAVID) website, whereas gene set enrichment analysis (GSEA) was performed with the R package phenoTest. The survival analysis was determined with the R package survivALL. Analyzing the expression data of more than 2500 primary BC, we ascertained that GPER levels are associated with pro-migratory and metastatic genes belonging to cell adhesion molecules (CAMs), extracellular matrix (ECM)-receptor interaction, and focal adhesion (FA) signaling pathways. Thereafter, evaluating the disease-free interval (DFI) in ER-negative BC patients, we found that the subjects expressing high GPER levels exhibited a shorter DFI in respect to those exhibiting low GPER levels. Overall, our results may pave the way to further dissect the network triggered by GPER in the breast malignancies lacking ER toward a better assessment of its prognostic significance and the action elicited in mediating the aggressive features of the aforementioned BC subtype.
Identifiants
pubmed: 32143514
pii: cells9030622
doi: 10.3390/cells9030622
pmc: PMC7140398
pii:
doi:
Substances chimiques
Estrogens
0
Receptors, Estrogen
0
Receptors, G-Protein-Coupled
0
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The Authors declare that they have no competing interests.
Références
J Hazard Mater. 2018 Aug 5;355:1-9
pubmed: 29758456
Oncotarget. 2015 Jun 10;6(16):14488-96
pubmed: 25895032
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Tumour Biol. 2014 Jun;35(6):5675-87
pubmed: 24584816
J Cell Sci. 2017 May 1;130(9):1612-1624
pubmed: 28302906
J Cancer Res Ther. 2018 Dec;14(Supplement):S1170-S1172
pubmed: 30539865
Cancers (Basel). 2017 Aug 23;9(9):
pubmed: 28832494
Int J Cancer. 2012 Feb 1;130(3):555-66
pubmed: 21387294
Front Med. 2015 Sep;9(3):322-30
pubmed: 26276037
Cells. 2018 Jul 28;7(8):
pubmed: 30060564
Cells. 2020 Jan 19;9(1):
pubmed: 31963820
Malays J Pathol. 2016 Aug;38(2):83-92
pubmed: 27568664
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Cancer Invest. 2009 Dec;27(10):1023-37
pubmed: 19909018
Cells. 2019 Mar 07;8(3):
pubmed: 30866584
Breast Cancer Res. 2012 Jun 06;14(3):R88
pubmed: 22673183
Cancer Res. 2007 Feb 15;67(4):1859-66
pubmed: 17308128
Cells. 2019 Dec 20;9(1):
pubmed: 31861892
Adv Exp Med Biol. 2016;936:73-91
pubmed: 27739043
Steroids. 2008 Oct;73(9-10):870-3
pubmed: 18289622
Microvasc Res. 2010 Jul;80(1):133-41
pubmed: 20153339
Adv Drug Deliv Rev. 2016 Feb 1;97:4-27
pubmed: 26562801
Environ Health Perspect. 2015 May;123(5):493-9
pubmed: 25616260
Breast Cancer Res Treat. 2014 Jul;146(2):273-85
pubmed: 24928526
Int J Oncol. 2017 Apr;50(4):1191-1200
pubmed: 28260049
Cancer Res. 2007 Sep 15;67(18):8439-43
pubmed: 17875680
Nat Rev Mol Cell Biol. 2014 Dec;15(12):802-12
pubmed: 25355505
J Steroid Biochem Mol Biol. 2018 Feb;176:4-15
pubmed: 28347854
Breast Cancer Res Treat. 2011 Jul;128(2):457-66
pubmed: 21607586
Am J Transl Res. 2016 Jun 15;8(6):2838-44
pubmed: 27398167
Breast Cancer Res Treat. 2011 Jul;128(1):7-21
pubmed: 21499686
J Clin Invest. 2015 May;125(5):2123-35
pubmed: 25893606
Nat Rev Mol Cell Biol. 2014 Dec;15(12):786-801
pubmed: 25415508
Clin Cancer Res. 2006 Nov 1;12(21):6359-66
pubmed: 17085646
Cells. 2019 Jun 14;8(6):
pubmed: 31207943
Dis Model Mech. 2011 Mar;4(2):165-78
pubmed: 21324931
Biomed Res Int. 2014;2014:606458
pubmed: 25126569
Breast Cancer Res Treat. 2014 May;145(1):61-71
pubmed: 24715381
Nat Commun. 2017 May 15;8:15321
pubmed: 28504269
Endocr Connect. 2019 Jun 1;8(6):661-671
pubmed: 30999280
Cell Mol Biol (Noisy-le-grand). 2018 May 15;64(6):42-47
pubmed: 29808799
Theranostics. 2018 Oct 6;8(18):5178-5199
pubmed: 30429893
Breast Cancer Res Treat. 2018 Jun;169(2):231-241
pubmed: 29380207
APMIS. 2014 Oct;122(10):976-84
pubmed: 24628533
Chem Res Toxicol. 2016 Mar 21;29(3):285-95
pubmed: 26914403
Reprod Med Biol. 2016 Dec 05;16(1):4-20
pubmed: 29259445
Breast Cancer Res Treat. 2012 May;133(1):257-65
pubmed: 22270936
J Steroid Biochem Mol Biol. 2018 Feb;176:38-48
pubmed: 28595943
Int J Mol Sci. 2018 Jul 10;19(7):
pubmed: 29996493
Clin Cancer Res. 2013 Apr 1;19(7):1681-92
pubmed: 23554355
Chin Med J (Engl). 2009 Nov 20;122(22):2763-9
pubmed: 19951611
Cancer Invest. 2013 Jun;31(5):309-15
pubmed: 23688258
Breast Cancer Res. 2013;15(4):R64
pubmed: 23947803
Oncotarget. 2017 Jan 3;8(1):215-227
pubmed: 27966446
Nature. 2015 Jul 9;523(7559):149-51
pubmed: 26156357
Oncol Rep. 2016 Jul;36(1):3-9
pubmed: 27121546
Endocr Relat Cancer. 2014 Oct;21(5):739-53
pubmed: 25012984
Mol Cell Endocrinol. 2015 Dec 15;418 Pt 3:240-4
pubmed: 25433206
Mol Cancer Res. 2014 Nov;12(11):1644-1654
pubmed: 25030371
Breast Cancer Res Treat. 2010 Aug;123(1):51-8
pubmed: 19902352
Adv Drug Deliv Rev. 2016 Feb 1;97:41-55
pubmed: 26743193
Am J Clin Pathol. 2015 Apr;143(4):540-6
pubmed: 25780006
Oncogene. 2013 Feb 7;32(6):678-88
pubmed: 22430216
J Exp Clin Cancer Res. 2019 Feb 6;38(1):58
pubmed: 30728047
Oncotarget. 2018 May 25;9(40):25946-25956
pubmed: 29899833
Breast Cancer Res. 2017 Dec 6;19(1):129
pubmed: 29212519
J Proteome Res. 2011 Mar 4;10(3):1110-25
pubmed: 21186846
Cancer Res. 2014 Aug 1;74(15):4053-64
pubmed: 24894716
Nat Commun. 2014 May 29;5:3887
pubmed: 24871328
J Exp Clin Cancer Res. 2018 Jul 28;37(1):175
pubmed: 30055645
Int J Oncol. 2019 Aug;55(2):391-404
pubmed: 31268154
Appl Immunohistochem Mol Morphol. 2012 Mar;20(2):159-64
pubmed: 22427740
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Histochem Cell Biol. 2018 Jan;149(1):15-30
pubmed: 29143117
Front Endocrinol (Lausanne). 2014 May 06;5:66
pubmed: 24834064
Cells. 2018 Oct 05;7(10):
pubmed: 30301152
Cancers (Basel). 2019 May 06;11(5):
pubmed: 31064120
Cells. 2020 Jan 12;9(1):
pubmed: 31940873
Cancer Treat Rev. 2012 Oct;38(6):698-707
pubmed: 22178455
Mol Endocrinol. 2009 Nov;23(11):1815-26
pubmed: 19749156
Breast Cancer Res Treat. 2010 Aug;123(1):87-96
pubmed: 19911269
Biochim Biophys Acta Mol Cell Res. 2018 Apr;1865(4):638-649
pubmed: 29378216
Cell. 2015 Oct 8;163(2):506-19
pubmed: 26451490
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925
Cancer Genomics Proteomics. 2019 May-Jun;16(3):147-153
pubmed: 31018945