Animals
Breast Neoplasms
/ metabolism
Cell Self Renewal
/ genetics
DNA-Binding Proteins
/ deficiency
Disease Models, Animal
Enzyme Activation
Female
Humans
Lung Neoplasms
/ secondary
Mammary Neoplasms, Animal
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplastic Stem Cells
RNA-Binding Proteins
/ genetics
Rad51 Recombinase
/ metabolism
Triple Negative Breast Neoplasms
/ metabolism
Up-Regulation
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 09 2020
15 09 2020
Historique:
received:
27
11
2019
revised:
31
03
2020
accepted:
09
07
2020
pubmed:
16
7
2020
medline:
15
1
2021
entrez:
16
7
2020
Statut:
ppublish
Résumé
RAD51-associated protein 1 (RAD51AP1) plays an integral role in homologous recombination by activating RAD51 recombinase. Homologous recombination is essential for preserving genome integrity and RAD51AP1 is critical for D-loop formation, a key step in homologous recombination. Although RAD51AP1 is involved in maintaining genomic stability, recent studies have shown that RAD51AP1 expression is significantly upregulated in human cancers. However, the functional role of RAD51AP1 in tumor growth and the underlying molecular mechanism(s) by which RAD51AP1 regulates tumorigenesis have not been fully understood. Here, we use Rad51ap1-knockout mice in genetically engineered mouse models of breast cancer to unravel the role of RAD51AP1 in tumor growth and metastasis. RAD51AP1 gene transcript was increased in both luminal estrogen receptor-positive breast cancer and basal triple-negative breast cancer, which is associated with poor prognosis. Conversely, knockdown of RAD51AP1 (RADP51AP1 KD) in breast cancer cell lines reduced tumor growth. Rad51ap1-deficient mice were protected from oncogene-driven spontaneous mouse mammary tumor growth and associated lung metastasis.
Identifiants
pubmed: 32665355
pii: 0008-5472.CAN-19-3713
doi: 10.1158/0008-5472.CAN-19-3713
pmc: PMC9400129
mid: NIHMS1626465
doi:
Substances chimiques
DNA-Binding Proteins
0
RNA-Binding Proteins
0
Rad51ap1 protein, mouse
0
Rad51 Recombinase
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3855-3866Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK123360
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
Références
Asian Pac J Cancer Prev. 2015;16(9):3667-71
pubmed: 25987019
Cancer Res. 2014 Feb 15;74(4):1166-78
pubmed: 24371223
Neoplasia. 2005 Aug;7(8):748-60
pubmed: 16207477
Mol Cell. 2007 Nov 9;28(3):482-90
pubmed: 17996711
Cancer Res. 2016 Jun 1;76(11):3224-35
pubmed: 27197203
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11236-40
pubmed: 7972041
Nature. 2015 Oct 1;526(7571):131-5
pubmed: 26416748
Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3070-4
pubmed: 1348364
Am J Pathol. 2011 Jul;179(1):2-11
pubmed: 21640330
Clin Cancer Res. 2008 Mar 1;14(5):1333-9
pubmed: 18316552
Cancer Res. 2014 May 15;74(10):2698-709
pubmed: 24638980
Nature. 2006 Dec 7;444(7120):756-60
pubmed: 17051156
Cell Res. 2008 Jan;18(1):134-47
pubmed: 18157161
Cancer Treat Rev. 2016 Sep;49:25-36
pubmed: 27434881
Cancer Res. 2008 Jun 15;68(12):4674-82
pubmed: 18559513
Nature. 2006 Jul 13;442(7099):153-8
pubmed: 16838012
Annu Rev Biochem. 2008;77:229-57
pubmed: 18275380
Cancer Res. 2008 Aug 15;68(16):6533-40
pubmed: 18701476
Mol Cell Biol. 2013 Oct;33(19):3920-35
pubmed: 23918800
Cancer Res. 2011 Nov 1;71(21):6654-64
pubmed: 21920899
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10578-82
pubmed: 1359541
Mol Cell. 2019 Oct 3;76(1):11-26.e7
pubmed: 31400850
DNA Repair (Amst). 2014 Dec;24:87-97
pubmed: 25288561
Oncogene. 2001 Jun 28;20(29):3814-23
pubmed: 11439345
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
pubmed: 12629218
Nat Genet. 1998 Nov;20(3):291-3
pubmed: 9806551
Nat Rev Mol Cell Biol. 2006 Feb;7(2):131-42
pubmed: 16493418
Cell Death Differ. 2012 May;19(5):768-78
pubmed: 22117197
Am J Pathol. 1997 Feb;150(2):483-95
pubmed: 9033265
Clin Cancer Res. 2006 Sep 15;12(18):5395-402
pubmed: 17000672
Mol Cell. 2007 Nov 9;28(3):468-81
pubmed: 17996710
Clin Cancer Res. 2010 Jun 15;16(12):3113-20
pubmed: 20530701
Cancer Res. 2006 Dec 15;66(24):11560-4
pubmed: 17178845
Am J Pathol. 2003 Nov;163(5):2113-26
pubmed: 14578209
Br J Cancer. 2006 Mar 13;94(5):692-7
pubmed: 16495928
Nat Commun. 2015 Apr 24;6:6910
pubmed: 25908435
Pancreas. 2011 Jul;40(5):730-9
pubmed: 21633318
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15853-8
pubmed: 14668450
Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3560-5
pubmed: 21307306
PLoS One. 2008 Jul 09;3(7):e2637
pubmed: 18612434
Cancer Res. 2000 Aug 1;60(15):4231-7
pubmed: 10945635
Nature. 2001 May 17;411(6835):366-74
pubmed: 11357144
Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2298-302
pubmed: 7892263
Cancer Biol Ther. 2016;17(1):1-10
pubmed: 26618281
Stem Cells. 2011 Mar;29(3):418-29
pubmed: 21308861
J Immunol. 2007 Sep 1;179(5):2851-9
pubmed: 17709499
Science. 2000 Mar 17;287(5460):2017-9
pubmed: 10720328
Breast Cancer Res. 2008;10(4):210
pubmed: 18671830
Cell. 1992 May 1;69(3):439-56
pubmed: 1581960
Genes Chromosomes Cancer. 2005 Jul;43(3):227-38
pubmed: 15846790