Molecular mechanisms of TWIST1-regulated transcription in EMT and cancer metastasis.
BRD8
NuRD
TIP60
TWIST1
acetylation
epithelial-to-mesenchymal transition
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 11 2023
06 11 2023
Historique:
revised:
23
08
2023
received:
28
01
2023
accepted:
25
08
2023
pmc-release:
08
09
2024
medline:
7
11
2023
pubmed:
8
9
2023
entrez:
8
9
2023
Statut:
ppublish
Résumé
TWIST1 induces epithelial-to-mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N-terminus antagonizes TWIST1-regulated gene expression, cancer growth and metastasis. TWIST1 interacts with both the NuRD complex and the NuA4/TIP60 complex (TIP60-Com) via its N-terminus. Non-acetylated TWIST1-K73/76 selectively interacts with and recruits NuRD to repress epithelial target gene transcription. Diacetylated TWIST1-acK73/76 binds BRD8, a component of TIP60-Com that also binds histone H4-acK5/8, to recruit TIP60-Com to activate mesenchymal target genes and MYC. Knockdown of BRD8 abolishes TWIST1 and TIP60-Com interaction and TIP60-Com recruitment to TWIST1-activated genes, resulting in decreasing TWIST1-activated target gene expression and cancer metastasis. Both TWIST1/NuRD and TWIST1/TIP60-Com complexes are required for TWIST1 to promote EMT, proliferation, and metastasis at full capacity. Therefore, the diacetylation status of TWIST1-K73/76 dictates whether TWIST1 interacts either with NuRD to repress epithelial genes, or with TIP60-Com to activate mesenchymal genes and MYC. Since BRD8 is essential for TWIST1-acK73/76 and TIP60-Com interaction, targeting BRD8 could be a means to inhibit TWIST1-activated gene expression.
Identifiants
pubmed: 37680145
doi: 10.15252/embr.202356902
pmc: PMC10626429
doi:
Substances chimiques
TWIST1 protein, human
0
Nuclear Proteins
0
Twist-Related Protein 1
0
Banques de données
GEO
['GSE189828']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e56902Subventions
Organisme : NCI NIH HHS
ID : R01 CA193455
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA267006
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NIDCR NIH HHS
ID : R21 DE033147
Pays : United States
Organisme : NIH HHS
ID : S10 OD028648
Pays : United States
Informations de copyright
© 2023 The Authors.
Références
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Genes Dev. 1995 Mar 15;9(6):686-99
pubmed: 7729687
EMBO J. 1999 Sep 15;18(18):5108-19
pubmed: 10487762
Cell Res. 2012 Jan;22(1):90-106
pubmed: 21876555
Cell Death Dis. 2020 Jul 9;11(7):520
pubmed: 32647142
J Biol Chem. 2016 May 27;291(22):11518-28
pubmed: 26975371
Cell. 2004 Jun 25;117(7):927-39
pubmed: 15210113
Mol Carcinog. 2016 May;55(5):941-52
pubmed: 26013710
EMBO Rep. 2023 Nov 6;24(11):e56902
pubmed: 37680145
Nature. 2009 Oct 1;461(7264):664-8
pubmed: 19794495
Nat Rev Cancer. 2012 Jun 22;12(7):465-77
pubmed: 22722403
Stem Cells. 2010 Aug;28(8):1435-45
pubmed: 20572012
Pathology. 2021 Feb;53(2):239-246
pubmed: 33036771
Mol Cell Biochem. 2021 Jun;476(6):2295-2306
pubmed: 33582945
Breast Cancer Res. 2012 Sep 11;14(5):R123
pubmed: 22967435
Cell. 2008 May 16;133(4):704-15
pubmed: 18485877
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11494-11499
pubmed: 29073077
Int J Oncol. 2009 Nov;35(5):1101-9
pubmed: 19787264
Cancer Res. 2011 Jan 1;71(1):245-54
pubmed: 21199805
Cell Res. 2011 Feb;21(2):275-89
pubmed: 20714342
Nat Struct Mol Biol. 2019 Oct;26(10):870-879
pubmed: 31582847
Breast Cancer Res. 2011;13(6):R112
pubmed: 22060274
Bioessays. 2009 Oct;31(10):1050-61
pubmed: 19722182
Mol Cell. 2016 May 5;62(3):409-421
pubmed: 27153538
Nucleic Acids Res. 2018 Jul 2;46(W1):W537-W544
pubmed: 29790989
Nat Genet. 1997 Jan;15(1):42-6
pubmed: 8988167
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Biosci. 2016 Jun;41(2):295-311
pubmed: 27240990
Oncogene. 2017 Feb 23;36(8):1157-1166
pubmed: 27524420
Epigenomics. 2015;7(8):1351-63
pubmed: 26638912
Int J Oncol. 2015 Apr;46(4):1461-72
pubmed: 25652255
Cancer Res. 2007 Mar 1;67(5):1979-87
pubmed: 17332325
Genes Dev. 2019 Aug 1;33(15-16):936-959
pubmed: 31123059
J Biol Chem. 1997 Nov 21;272(47):29834-41
pubmed: 9368056
Nat Cell Biol. 2010 Oct;12(10):982-92
pubmed: 20818389
Cancer Cell. 2014 Feb 10;25(2):210-25
pubmed: 24525235
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7297-301
pubmed: 7638184
Epigenetics Chromatin. 2015 Nov 06;8:45
pubmed: 26550034
Nat Genet. 1997 Jan;15(1):36-41
pubmed: 8988166
Nature. 2010 Dec 23;468(7327):1067-73
pubmed: 20871596
Int J Biol Sci. 2014 Mar 15;10(4):396-403
pubmed: 24719557
Nat Rev Mol Cell Biol. 2017 Apr;18(4):246-262
pubmed: 28053347
Oncogene. 2007 Aug 13;26(37):5395-407
pubmed: 17694081
Mol Cell Endocrinol. 2021 Mar 15;524:111169
pubmed: 33476703
Mol Cell Biol. 2004 Mar;24(5):1884-96
pubmed: 14966270
J Cancer. 2015 Oct 29;6(12):1331-6
pubmed: 26640593
Nat Commun. 2014 Aug 22;5:4697
pubmed: 25146389
Cancer Res. 2011 Jun 1;71(11):3980-90
pubmed: 21502402
Oncogenesis. 2017 May 8;6(5):e330
pubmed: 28481366
Cancer Res. 2002 Mar 15;62(6):1613-8
pubmed: 11912130
Int J Biochem Cell Biol. 2016 Feb;71:62-71
pubmed: 26693891
Genes Dev. 1999 Sep 1;13(17):2207-17
pubmed: 10485844
Am J Pathol. 2013 Oct;183(4):1281-1292
pubmed: 23906809
Cancer Cell. 2011 Mar 8;19(3):372-86
pubmed: 21397860
Cell. 2012 Mar 30;149(1):214-31
pubmed: 22464331
Mol Endocrinol. 1999 Oct;13(10):1695-703
pubmed: 10517671
Nat Rev Cancer. 2021 May;21(5):325-338
pubmed: 33547455
Int J Biol Sci. 2012;8(4):522-32
pubmed: 22457607
Sci Transl Med. 2019 Mar 20;11(484):
pubmed: 30894502
EMBO J. 2014 Jun 17;33(12):1397-415
pubmed: 24843044