Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
28 02 2023
28 02 2023
Historique:
received:
10
08
2022
accepted:
10
02
2023
revised:
08
02
2023
entrez:
28
2
2023
pubmed:
1
3
2023
medline:
3
3
2023
Statut:
epublish
Résumé
Notch signaling is a conserved signaling pathway that participates in many aspects of mammary gland development and homeostasis, and has extensively been associated with breast tumorigenesis. Here, to unravel the as yet debated role of Notch3 in breast cancer development, we investigated its expression in human breast cancer samples and effects of its loss in mice. Notch3 expression was very weak in breast cancer cells and was associated with good patient prognosis. Interestingly, its expression was very strong in stromal cells of these patients, though this had no prognostic value. Mechanistically, we demonstrated that Notch3 prevents tumor initiation via HeyL-mediated inhibition of Mybl2, an important regulator of cell cycle. In the mammary glands of Notch3-deficient mice, we observed accelerated tumor initiation and proliferation in a MMTV-Neu model. Notch3-null tumors were enriched in Mybl2 mRNA signature and protein expression. Hence, our study reinforces the anti-tumoral role of Notch3 in breast tumorigenesis.
Identifiants
pubmed: 36854682
doi: 10.1038/s41419-023-05674-7
pii: 10.1038/s41419-023-05674-7
pmc: PMC9975231
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Cell Cycle Proteins
0
HEYL protein, human
0
Heyl protein, mouse
0
MYBL2 protein, human
0
NOTCH3 protein, human
0
Receptor, Notch3
0
Repressor Proteins
0
Trans-Activators
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
171Informations de copyright
© 2023. The Author(s).
Références
Nat Rev Cancer. 2017 Mar;17(3):145-159
pubmed: 28154375
J Exp Med. 1998 Aug 3;188(3):589-96
pubmed: 9687535
Nature. 2012 Oct 4;490(7418):61-70
pubmed: 23000897
Cell Death Dis. 2017 Jun 22;8(6):e2895
pubmed: 28640249
Nat Med. 2021 May;27(5):820-832
pubmed: 33958794
Cancer Res. 2017 Mar 15;77(6):1439-1452
pubmed: 28108512
Cancer Cell. 2018 Oct 8;34(4):536-548
pubmed: 30146333
Oncogene. 1997 Apr 24;14(16):1883-90
pubmed: 9150355
Breast Cancer Res. 2018 Sep 4;20(1):105
pubmed: 30180881
Cancer Cell. 2014 Mar 17;25(3):318-34
pubmed: 24651013
Oncogenesis. 2018 Aug 13;7(8):59
pubmed: 30100605
Genes Dev. 1992 Mar;6(3):345-55
pubmed: 1372276
Cancer Res. 2006 Feb 1;66(3):1517-25
pubmed: 16452208
Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188407
pubmed: 32853735
Mol Cell Oncol. 2016 Sep 12;3(6):e1232186
pubmed: 28090578
Cancer Res. 2009 Jun 15;69(12):5015-22
pubmed: 19491273
Cancer Res. 2008 Mar 15;68(6):1881-8
pubmed: 18339869
Cell Death Dis. 2021 May 18;12(6):502
pubmed: 34006834
PLoS Genet. 2012;8(5):e1002728
pubmed: 22615585
Annu Rev Pathol. 2017 Jan 24;12:245-275
pubmed: 27959635
Cell Stem Cell. 2013 Jul 3;13(1):48-61
pubmed: 23684539
Cell Stem Cell. 2010 Sep 3;7(3):403-17
pubmed: 20804975
Biochim Biophys Acta. 2014 Sep;1839(9):813-25
pubmed: 24984200
Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4856-61
pubmed: 18347334
Dev Cell. 2017 May 8;41(3):228-241
pubmed: 28486129
Am J Pathol. 2006 Mar;168(3):973-90
pubmed: 16507912
Oncogene. 2012 Feb 16;31(7):907-17
pubmed: 21743488
J Cell Biol. 2013 Oct 14;203(1):47-56
pubmed: 24100291
Cancer Cell. 2003 Mar;3(3):203-5
pubmed: 12676578
J Dev Biol. 2016 Mar 1;4(1):4
pubmed: 27110512
Cell. 2014 Oct 23;159(3):499-513
pubmed: 25417103
Cancer Res. 2013 Jun 1;73(11):3451-9
pubmed: 23610446
Exp Cell Res. 2020 Jan 15;386(2):111743
pubmed: 31770532