Metabolic Reprogramming of Mammary Epithelial Cells during TGF-β-Induced Epithelial-to-Mesenchymal Transition.
NMuMG breast cells
TGF-β
choline kinase α (CHKα)
epithelial-to-mesenchymal transition (EMT)
metabolism
Journal
Metabolites
ISSN: 2218-1989
Titre abrégé: Metabolites
Pays: Switzerland
ID NLM: 101578790
Informations de publication
Date de publication:
15 Sep 2021
15 Sep 2021
Historique:
received:
09
07
2021
revised:
30
08
2021
accepted:
04
09
2021
entrez:
26
9
2021
pubmed:
27
9
2021
medline:
27
9
2021
Statut:
epublish
Résumé
The cytokine transforming growth factor-β (TGF-β) can induce normal breast epithelial cells to take on a mesenchymal phenotype, termed epithelial-to-mesenchymal transition (EMT). While the transcriptional and proteomic changes during TGF-β-induced EMT have been described, the metabolic rewiring that occurs in epithelial cells undergoing EMT is not well understood. Here, we quantitively analyzed the TGF-β-induced metabolic reprogramming during EMT of non-transformed NMuMG mouse mammary gland epithelial cells using nuclear magnetic resonance (NMR) spectroscopy. We found that TGF-β elevates glycolytic and tricarboxylic acid (TCA)-cycle activity and increases glutaminolysis. Additionally, TGF-β affects the hexosamine pathway, arginine-proline metabolism, the cellular redox state, and strongly affects choline metabolism during EMT. TGF-β was found to induce phosphocholine production. A kinase inhibitor RSM-93A that inhibits choline kinase α (CHKα) mitigated TGF-β-induced changes associated with EMT, i.e., increased filamentous (F)-actin stress fiber formation and N-Cadherin mesenchymal marker expression.
Identifiants
pubmed: 34564442
pii: metabo11090626
doi: 10.3390/metabo11090626
pmc: PMC8464788
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Centre for Cancer Genomics Netherlands
ID : CGC.NL
Organisme : Chinese scholarship council
ID : CSC
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
FEBS J. 2017 Oct;284(20):3437-3454
pubmed: 28834297
Nat Commun. 2017 May 11;8:15267
pubmed: 28492237
Oncogene. 2002 Jun 20;21(27):4317-22
pubmed: 12082619
Nat Commun. 2014 Mar 03;5:3388
pubmed: 24584437
J Cell Physiol. 2002 Apr;191(1):1-16
pubmed: 11920677
Dev Cell. 2008 Jun;14(6):818-29
pubmed: 18539112
Nat Rev Cancer. 2002 Jun;2(6):442-54
pubmed: 12189386
Nucleic Acids Res. 1999 Jan 1;27(1):29-34
pubmed: 9847135
Mol Cell. 2013 Sep 12;51(5):559-72
pubmed: 23973329
Antioxid Redox Signal. 2019 Feb 1;30(4):635-649
pubmed: 28990419
Sci Rep. 2016 Nov 08;6:36289
pubmed: 27824159
Nat Rev Mol Cell Biol. 2018 Jul;19(7):419-435
pubmed: 29643418
J Natl Cancer Inst. 2015 Dec 11;108(5):
pubmed: 26657335
Breast Cancer Res. 2003;5(6):R187-98
pubmed: 14580254
Nature. 2017 Jul 6;547(7661):109-113
pubmed: 28658205
Cancer Metab. 2016 Oct 17;4:19
pubmed: 27777765
Curr Opin Genet Dev. 2011 Feb;21(1):93-9
pubmed: 21251810
Sci Adv. 2019 Nov 27;5(11):eaax7525
pubmed: 31807705
Cell. 2013 Aug 1;154(3):651-63
pubmed: 23911327
Dev Dyn. 2018 Mar;247(3):473-480
pubmed: 28795450
Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):16105-16110
pubmed: 31341083
J Clin Invest. 2009 Jun;119(6):1420-8
pubmed: 19487818
Nature. 2020 Jan;577(7791):566-571
pubmed: 31915377
EMBO J. 2020 Apr 15;39(8):e103334
pubmed: 32134147
Nat Rev Cancer. 2004 Nov;4(11):891-9
pubmed: 15516961
Cancer Metastasis Rev. 2012 Dec;31(3-4):553-68
pubmed: 22714591
Cancers (Basel). 2018 Oct 22;10(10):
pubmed: 30360374
Trends Cancer. 2017 Jan;3(1):56-71
pubmed: 28718426
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15526-31
pubmed: 25313085
Nat Rev Mol Cell Biol. 2012 Oct;13(10):616-30
pubmed: 22992590
Biochem Biophys Res Commun. 2002 Aug 23;296(3):580-3
pubmed: 12176020
FEBS J. 2017 Oct;284(19):3132-3144
pubmed: 28444969
Nat Rev Cancer. 2018 Nov;18(11):681-695
pubmed: 30181570
Oncotarget. 2018 Jun 29;9(50):29468-29483
pubmed: 30034631
Front Oncol. 2017 Mar 14;7:40
pubmed: 28352611
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
pubmed: 24556840
Oncogenesis. 2013;2:e38
pubmed: 25522435
Transl Oncol. 2016 Dec;9(6):512-520
pubmed: 27816688
Cell. 2008 Jul 25;134(2):215-30
pubmed: 18662538
Anal Chim Acta. 2017 Aug 8;980:1-24
pubmed: 28622799
Nat Rev Cancer. 2013 Feb;13(2):97-110
pubmed: 23344542
Curr Opin Cell Biol. 2018 Apr;51:1-7
pubmed: 29149681
Cell Tissue Res. 2002 Jan;307(1):1-14
pubmed: 11810309
Prog Lipid Res. 2016 Jul;63:28-40
pubmed: 27073147
Cell Death Differ. 2017 Jan;24(1):1-2
pubmed: 27886164
Cell Mol Life Sci. 2020 Jun;77(11):2103-2123
pubmed: 31822964
Oncotarget. 2016 Nov 8;7(45):73414-73431
pubmed: 27705917
Cold Spring Harb Perspect Biol. 2018 Mar 1;10(3):
pubmed: 28289061