Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
19 10 2021
19 10 2021
Historique:
received:
10
05
2021
revised:
04
08
2021
accepted:
30
08
2021
pubmed:
5
9
2021
medline:
3
11
2021
entrez:
4
9
2021
Statut:
ppublish
Résumé
Epithelial-mesenchymal transition (EMT), a basic developmental process that might promote cancer metastasis, has been studied from various perspectives. Recently, the early warning theory has been used to anticipate critical transitions in EMT from mathematical modeling. However, the underlying mechanisms of EMT involving complex molecular networks remain to be clarified. Especially, how to quantify the global stability and stochastic transition dynamics of EMT and what the underlying mechanism for early warning theory in EMT is remain to be fully clarified. To address these issues, we constructed a comprehensive gene regulatory network model for EMT and quantified the corresponding potential landscape. The landscape for EMT displays multiple stable attractors, which correspond to E, M, and some other intermediate states. Based on the path-integral approach, we identified the most probable transition paths of EMT, which are supported by experimental data. Correspondingly, the results of transition actions demonstrated that intermediate states can accelerate EMT, consistent with recent studies. By integrating the landscape and path with early warning concept, we identified the potential barrier height from the landscape as a global and more accurate measure for early warning signals to predict critical transitions in EMT. The landscape results also provide an intuitive and quantitative explanation for the early warning theory. Overall, the landscape and path results advance our mechanistic understanding of dynamical transitions and roles of intermediate states in EMT, and the potential barrier height provides a new, to our knowledge, measure for critical transitions and quantitative explanations for the early warning theory.
Identifiants
pubmed: 34480928
pii: S0006-3495(21)00729-3
doi: 10.1016/j.bpj.2021.08.043
pmc: PMC8553640
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4484-4500Informations de copyright
Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Références
Cancer Res. 2014 Nov 1;74(21):5963-77
pubmed: 25189528
Cancer Res. 2017 Mar 1;77(5):1063-1074
pubmed: 27932399
Ecol Lett. 2008 Feb;11(2):128-38
pubmed: 18021242
Nat Rev Cancer. 2014 May;14(5):371-80
pubmed: 24739582
Sci China Life Sci. 2017 Jun;60(6):627-646
pubmed: 28646471
Nat Commun. 2017 Aug 4;8(1):198
pubmed: 28775339
Am J Transl Res. 2010 Mar 25;2(2):170-80
pubmed: 20407606
Int J Mol Med. 2015 Feb;35(2):311-8
pubmed: 25421593
PLoS One. 2012;7(7):e41010
pubmed: 22815897
Oncogene. 2007 Oct 25;26(49):6979-88
pubmed: 17486063
Science. 2011 May 27;332(6033):1079-82
pubmed: 21527677
J R Soc Interface. 2012 Oct 7;9(75):2527-39
pubmed: 22593100
Annu Rev Biophys. 2020 May 6;49:1-18
pubmed: 31913665
J Chem Phys. 2008 Mar 14;128(10):104111
pubmed: 18345881
Biophys J. 2013 Aug 20;105(4):1079-89
pubmed: 23972859
Am Nat. 2011 Oct;178(4):442-51
pubmed: 21956023
Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12271-6
pubmed: 18719111
PLoS Comput Biol. 2013;9(8):e1003165
pubmed: 23935477
Phys Chem Chem Phys. 2017 Mar 15;19(11):7642-7651
pubmed: 28256642
Sci Rep. 2012;2:342
pubmed: 22461973
Nat Rev Genet. 2005 Jun;6(6):451-64
pubmed: 15883588
PLoS Comput Biol. 2007 Oct;3(10):1871-78
pubmed: 17922568
Front Oncol. 2015 Jul 20;5:155
pubmed: 26258068
Sci Signal. 2014 Sep 30;7(345):ra91
pubmed: 25270257
J Clin Invest. 2009 Jun;119(6):1420-8
pubmed: 19487818
J Chem Phys. 2010 Sep 28;133(12):125103
pubmed: 20886967
Front Genet. 2021 Jan 08;11:604585
pubmed: 33488673
BMC Syst Biol. 2018 Jun 13;12(1):67
pubmed: 29898720
Cancer Res. 2015 Jul 1;75(13):2607-18
pubmed: 25972342
Phys Chem Chem Phys. 2016 Jul 21;18(27):17949-56
pubmed: 27328302
Proc Natl Acad Sci U S A. 2019 Dec 16;:
pubmed: 31843939
Curr Opin Biotechnol. 2015 Aug;34:48-55
pubmed: 25498477
Proc Natl Acad Sci U S A. 2011 May 17;108(20):8257-62
pubmed: 21536909
Curr Opin Syst Biol. 2018 Jun;9:32-41
pubmed: 30450444
NPJ Syst Biol Appl. 2018 Aug 23;4:34
pubmed: 30155271
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10185-90
pubmed: 24946805
Phys Rev Lett. 2014 Aug 15;113(7):078102
pubmed: 25170733
BMC Syst Biol. 2017 Feb 16;11(1):24
pubmed: 28209158
NPJ Syst Biol Appl. 2020 May 18;6(1):15
pubmed: 32424264
Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6716-21
pubmed: 10359778
PLoS Comput Biol. 2015 Mar 20;11(3):e1004156
pubmed: 25794282
Nature. 2008 Feb 21;451(7181):893-5
pubmed: 18288170
Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14130-5
pubmed: 25228772
Nature. 2011 Dec 25;481(7381):357-9
pubmed: 22198671
Bioinformatics. 2019 Aug 1;35(15):2593-2601
pubmed: 30535348
Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):11883-11890
pubmed: 30373844
Nat Rev Mol Cell Biol. 2003 Aug;4(8):657-65
pubmed: 12923528
Phys Biol. 2019 Jan 18;16(2):021001
pubmed: 30560804
PLoS Comput Biol. 2015 Nov 03;11(11):e1004571
pubmed: 26528548
Nat Rev Cancer. 2002 Jun;2(6):442-54
pubmed: 12189386
BMC Syst Biol. 2014 May 15;8:55
pubmed: 24886091
Nature. 2018 Apr;556(7702):463-468
pubmed: 29670281
Science. 2012 Oct 19;338(6105):344-8
pubmed: 23087241
NPJ Syst Biol Appl. 2015 Nov 26;1:15014
pubmed: 28725463
Bioinformatics. 2017 Jul 15;33(14):i102-i109
pubmed: 28881967
PLoS Comput Biol. 2017 Mar 31;13(3):e1005456
pubmed: 28362798
Science. 2012 Jun 1;336(6085):1175-7
pubmed: 22654061
Cells Tissues Organs. 2021 Feb 10;:1-14
pubmed: 33567424
Phys Rev E. 2016 Nov;94(5-1):052150
pubmed: 27967115
Ecol Lett. 2008 May;11(5):450-60
pubmed: 18279354
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2374-9
pubmed: 12606710
Nat Commun. 2018 Nov 27;9(1):5005
pubmed: 30479345
Kidney Int. 2002 Jul;62(1):137-46
pubmed: 12081572
Phys Rev X. 2015 Jul-Sep;5:
pubmed: 26451275
Chaos. 2012 Jun;22(2):023140
pubmed: 22757547
PLoS Comput Biol. 2015 Nov 10;11(11):e1004569
pubmed: 26554584
Biochim Biophys Acta Rev Cancer. 2017 Apr;1867(2):167-175
pubmed: 28396217
Sci Rep. 2017 Mar 23;7:44988
pubmed: 28332555
Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):5902-5907
pubmed: 29784817
Adv Sci (Weinh). 2021 Mar 18;8(10):2003133
pubmed: 34026435
Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18144-9
pubmed: 24154725
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12795-800
pubmed: 12237400
Oncotarget. 2015 Sep 22;6(28):25161-74
pubmed: 26317796
PLoS Comput Biol. 2020 Mar 10;16(3):e1007682
pubmed: 32155144