S-adenosylmethionine biosynthesis is a targetable metabolic vulnerability of cancer stem cells.
Animals
Apoptosis
CD24 Antigen
Cell Line, Tumor
Disease Models, Animal
Gene Silencing
Histones
/ metabolism
Humans
Hyaluronan Receptors
Mass Spectrometry
Methionine
/ metabolism
Methionine Adenosyltransferase
/ genetics
Mice
Neoplasms
/ genetics
Neoplastic Stem Cells
/ metabolism
S-Adenosylmethionine
/ metabolism
Breast cancer
Cancer stem cell
Methionine
Nutrition
S-adenosylmethionine
Therapeutics
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
19
09
2018
accepted:
22
01
2019
pubmed:
4
2
2019
medline:
21
8
2019
entrez:
4
2
2019
Statut:
ppublish
Résumé
Many transformed cells and embryonic stem cells are dependent on the biosynthesis of the universal methyl-donor S-adenosylmethionine (SAM) from methionine by the enzyme MAT2A to maintain their epigenome. We hypothesized that cancer stem cells (CSCs) rely on SAM biosynthesis and that the combination of methionine depletion and MAT2A inhibition would eradicate CSCs. Human triple (ER/PR/HER2)-negative breast carcinoma (TNBC) cell lines were cultured as CSC-enriched mammospheres in control or methionine-free media. MAT2A was inhibited with siRNAs or cycloleucine. The effects of methionine restriction and/or MAT2A inhibition on the formation of mammospheres, the expression of CSC markers (CD44 Methionine restriction inhibited mammosphere formation and reduced the CD44 Our findings point to SAM biosynthesis as a unique metabolic vulnerability of CSCs that can be targeted by combining methionine depletion with MAT2A inhibition to eradicate drug-resistant CSCs.
Identifiants
pubmed: 30712196
doi: 10.1007/s10549-019-05146-7
pii: 10.1007/s10549-019-05146-7
pmc: PMC6494685
mid: NIHMS1520613
doi:
Substances chimiques
CD24 Antigen
0
Histones
0
Hyaluronan Receptors
0
S-Adenosylmethionine
7LP2MPO46S
Methionine
AE28F7PNPL
MAT2A protein, human
EC 2.5.1.6
Methionine Adenosyltransferase
EC 2.5.1.6
Types de publication
Journal Article
Langues
eng
Pagination
39-50Subventions
Organisme : National Institute of General Medical Sciences
ID : P41GM108538
Organisme : Morgridge Institute
ID : (JJC)
Organisme : NCI NIH HHS
ID : P30 CA014520
Pays : United States
Organisme : Breast Cancer Research Foundation
ID : (VLC)
Organisme : V Foundation for Cancer Research
ID : (VLC)
Organisme : National Cancer Institute
ID : P30CA14520
Organisme : University of Wisconsin Carbone Cancer Center
ID : Pilot Project
Organisme : NIGMS NIH HHS
ID : P41 GM108538
Pays : United States
Organisme : Wisconsin Partnership Program
ID : (VLC)
Organisme : Sidney Kimmel Foundation for Cancer Research
ID : (PWL)
Références
Nutr Cancer. 2002;42(2):158-66
pubmed: 12416254
Int J Oncol. 2003 Feb;22(2):415-20
pubmed: 12527942
J Biol Chem. 2003 May 30;278(22):19885-90
pubmed: 12660248
J Clin Invest. 2006 Jan;116(1):261-70
pubmed: 16395408
Hepatol Res. 2007 May;37(5):376-88
pubmed: 17441811
Anticancer Res. 2007 Jul-Aug;27(4C):2779-83
pubmed: 17695447
Oncology. 2010;78(3-4):205-9
pubmed: 20424491
Oncogene. 2011 May 5;30(18):2161-72
pubmed: 21242971
Biochem J. 2011 Jun 1;436(2):507-16
pubmed: 21406062
Mol Cancer Ther. 2011 Jun;10(6):1113-23
pubmed: 21460102
Cell. 2011 Apr 15;145(2):183-97
pubmed: 21477851
Clin Cancer Res. 2011 Aug 1;17(15):5005-15
pubmed: 21653692
Science. 2013 Jan 11;339(6116):222-6
pubmed: 23118012
Nat Rev Cancer. 2013 Aug;13(8):572-83
pubmed: 23822983
Clin Cancer Res. 2014 Jan 1;20(1):56-67
pubmed: 24132917
Cell Metab. 2014 May 6;19(5):780-94
pubmed: 24746804
Diabetes. 2014 Nov;63(11):3721-33
pubmed: 24947368
Oncogene. 2015 Nov 5;34(45):5626-34
pubmed: 25684139
Clin Cancer Res. 2015 Jun 15;21(12):2780-91
pubmed: 25724522
Cell Metab. 2015 Nov 3;22(5):861-73
pubmed: 26411344
Oncotarget. 2016 Mar 22;7(12):13902-16
pubmed: 26418898
Science. 2016 May 13;352(6287):844-9
pubmed: 27174990
Nat Rev Clin Oncol. 2017 Oct;14(10):611-629
pubmed: 28397828
Proc Natl Acad Sci U S A. 2017 May 30;114(22):E4482-E4491
pubmed: 28507152
Nat Chem Biol. 2017 Jul;13(7):785-792
pubmed: 28553945
Nat Commun. 2017 Oct 30;8(1):1193
pubmed: 29084956
Exp Biol Med (Maywood). 2018 Jan;243(2):107-117
pubmed: 29141455
Cell Rep. 2017 Dec 5;21(10):2965-2977
pubmed: 29212039
FASEB J. 2018 Jun;32(6):3471-3482
pubmed: 29401631
Cancer Res. 1979 Jun;39(6 Pt 1):2204-10
pubmed: 445419
Proc Natl Acad Sci U S A. 1974 Apr;71(4):1133-6
pubmed: 4524624
Mol Pharmacol. 1979 May;15(3):661-77
pubmed: 492150
Neuropathol Appl Neurobiol. 1980 Sep-Oct;6(5):349-60
pubmed: 6256679
Biochem Biophys Res Commun. 1983 Dec 16;117(2):429-34
pubmed: 6661235
Cancer Res. 1980 Mar;40(3):634-41
pubmed: 6937240
Cancer Treat Rep. 1981 Jan-Feb;65(1-2):21-7
pubmed: 7013976
Anticancer Res. 1995 May-Jun;15(3):717-8
pubmed: 7645948
Cancer Res. 1993 Dec 1;53(23):5676-9
pubmed: 8242623