Unravelling the clinicopathological and functional significance of replication protein A (RPA) heterotrimeric complex in breast cancers.
Journal
NPJ breast cancer
ISSN: 2374-4677
Titre abrégé: NPJ Breast Cancer
Pays: United States
ID NLM: 101674891
Informations de publication
Date de publication:
30 Mar 2023
30 Mar 2023
Historique:
medline:
31
3
2023
entrez:
30
3
2023
pubmed:
31
3
2023
Statut:
epublish
Résumé
Replication Protein A (RPA), a heterotrimeric complex consisting of RPA1, 2, and 3 subunits, is a single-stranded DNA (ssDNA)-binding protein that is critically involved in replication, checkpoint regulation and DNA repair. Here we have evaluated RPA in 776 pure ductal carcinomas in situ (DCIS), 239 DCIS that co-exist with invasive breast cancer (IBC), 50 normal breast tissue and 4221 IBC. Transcriptomic [METABRIC cohort (n = 1980)] and genomic [TCGA cohort (n = 1090)] evaluations were completed. Preclinically, RPA deficient cells were tested for cisplatin sensitivity and Olaparib induced synthetic lethality. Low RPA linked to aggressive DCIS, aggressive IBC, and shorter survival outcomes. At the transcriptomic level, low RPA tumours overexpress pseudogene/lncRNA as well as genes involved in chemical carcinogenesis, and drug metabolism. Low RPA remains linked with poor outcome. RPA deficient cells are sensitive to cisplatin and Olaparib induced synthetic lethality. We conclude that RPA directed precision oncology strategy is feasible in breast cancers.
Identifiants
pubmed: 36997566
doi: 10.1038/s41523-023-00524-3
pii: 10.1038/s41523-023-00524-3
pmc: PMC10063624
doi:
Types de publication
Journal Article
Langues
eng
Pagination
18Informations de copyright
© 2023. The Author(s).
Références
Clin Cancer Res. 2002 Mar;8(3):752-8
pubmed: 11895905
Breast Cancer Res Treat. 2015 Jan;149(2):353-62
pubmed: 25528020
Breast Cancer Res Treat. 2014 Feb;143(3):411-21
pubmed: 24381055
Breast Cancer Res Treat. 2010 Oct;123(3):725-31
pubmed: 20020197
J BUON. 2020 May-Jun;25(3):1482-1489
pubmed: 32862594
Nucleic Acids Res. 2006;34(15):4126-37
pubmed: 16935876
Panminerva Med. 2015 Dec;57(4):183-9
pubmed: 26824734
Mod Pathol. 2017 Jul;30(7):952-963
pubmed: 28338653
Cancers (Basel). 2020 Mar 06;12(3):
pubmed: 32155777
Oncol Lett. 2020 Mar;19(3):1831-1841
pubmed: 32194677
NPJ Breast Cancer. 2022 Mar 4;8(1):28
pubmed: 35246547
Clin Breast Cancer. 2021 Feb;21(1):57-73.e7
pubmed: 32919863
Cancer Res. 2018 Dec 15;78(24):6818-6827
pubmed: 30297533
Mol Oncol. 2015 Mar;9(3):569-85
pubmed: 25468710
Mol Oncol. 2016 Feb;10(2):213-23
pubmed: 26459098
J Natl Cancer Inst. 2005 Aug 17;97(16):1180-4
pubmed: 16106022
Breast Cancer Res Treat. 2013 Dec;142(3):515-27
pubmed: 24253812
Mol Oncol. 2015 Jan;9(1):204-17
pubmed: 25205036
Cell Death Dis. 2014 Sep 11;5:e1411
pubmed: 25210794
Epigenetics Chromatin. 2019 Dec 5;12(1):71
pubmed: 31805986
Curr Opin Struct Biol. 2004 Feb;14(1):36-42
pubmed: 15102447
Cell. 2002 Aug 9;110(3):277-80
pubmed: 12176313
Genome Biol. 2014;15(12):550
pubmed: 25516281
NAR Cancer. 2020 Sep 25;2(3):zcaa022
pubmed: 34316690
Nat Genet. 2005 Jul;37(7):750-5
pubmed: 15965476
Cell Biochem Biophys. 2013 Sep;67(1):175-80
pubmed: 23420526
Crit Rev Biochem Mol Biol. 1999;34(3):141-80
pubmed: 10473346
FEBS J. 2009 Feb;276(4):943-63
pubmed: 19154342
Br J Cancer. 2020 Apr;122(9):1277-1287
pubmed: 32047295
J Cell Physiol. 2006 Aug;208(2):267-73
pubmed: 16523492
Nature. 2015 Feb 26;518(7540):495-501
pubmed: 25719666
J Mol Biol. 2019 Jan 18;431(2):258-272
pubmed: 30428301
BJU Int. 2011 Jul;108(2 Pt 2):E59-65
pubmed: 21062395
Nat Rev Genet. 2009 Oct;10(10):691-703
pubmed: 19763152
Mod Pathol. 2007 Feb;20(2):159-66
pubmed: 17361204
Mol Oncol. 2014 May;8(3):520-32
pubmed: 24462520
Mol Cancer Ther. 2015 Apr;14(4):1057-65
pubmed: 25673821
Hum Pathol. 2011 Oct;42(10):1545-53
pubmed: 21496876
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Breast Cancer Res Treat. 2013 Jun;139(2):301-10
pubmed: 23624778
BMJ. 2012 Feb 29;344:e797
pubmed: 22378935
Cancer Res. 2013 Mar 1;73(5):1621-34
pubmed: 23253910
Semin Cell Dev Biol. 2019 Feb;86:112-120
pubmed: 29665433
Dig Dis Sci. 2017 Sep;62(9):2369-2375
pubmed: 28766245
Mol Cell. 2019 Sep 19;75(6):1286-1298.e12
pubmed: 31473101
Biochem Pharmacol. 2011 Jan 1;81(1):60-70
pubmed: 20854796
Nat Struct Mol Biol. 2018 Jun;25(6):446-453
pubmed: 29807999
Dig Dis. 2018;36(1):26-32
pubmed: 28683444
Breast Cancer Res Treat. 2016 Aug;159(1):41-53
pubmed: 27464795