Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 10 2023
06 10 2023
Historique:
received:
16
07
2022
accepted:
20
09
2023
medline:
9
10
2023
pubmed:
7
10
2023
entrez:
6
10
2023
Statut:
epublish
Résumé
Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings.
Identifiants
pubmed: 37803016
doi: 10.1038/s41467-023-41952-w
pii: 10.1038/s41467-023-41952-w
pmc: PMC10558488
doi:
Substances chimiques
Vitamin B Complex
12001-76-2
Niacin
2679MF687A
Pyridoxine
KV2JZ1BI6Z
Vitamin B 6
8059-24-3
Glycine
TE7660XO1C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6246Informations de copyright
© 2023. Springer Nature Limited.
Références
Nat Commun. 2023 Apr 3;14(1):1849
pubmed: 37012289
J Cancer Res Clin Oncol. 2007 Jul;133(7):477-85
pubmed: 17356858
PLoS One. 2013 Sep 20;8(9):e75312
pubmed: 24073261
Metabolites. 2021 Dec 01;11(12):
pubmed: 34940589
PLoS Comput Biol. 2019 Dec 23;15(12):e1007569
pubmed: 31869345
Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7697-E7706
pubmed: 28847964
J Immunol. 2014 Jan 1;192(1):136-44
pubmed: 24273001
PLoS Biol. 2021 Oct 26;19(10):e3001416
pubmed: 34699521
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W652-60
pubmed: 19429898
Clin Nutr. 2014 Jun;33(3):448-58
pubmed: 23835111
Nutrients. 2019 Aug 03;11(8):
pubmed: 31382615
Jpn J Cancer Res. 1998 Jun;89(6):649-56
pubmed: 9703363
Eur J Cancer. 2006 Jan;42(1):31-41
pubmed: 16314085
Cell Metab. 2014 Dec 2;20(6):1076-87
pubmed: 25470552
J Clin Exp Hepatol. 2017 Dec;7(4):340-357
pubmed: 29234200
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Front Cell Dev Biol. 2021 Apr 29;9:664553
pubmed: 33996820
Bioinformatics. 2014 Mar 15;30(6):801-7
pubmed: 22321699
Nat Rev Cancer. 2012 Nov;12(11):741-52
pubmed: 23018234
J Biol Chem. 2006 Jun 16;281(24):16768-76
pubmed: 16608839
Lancet Oncol. 2011 May;12(5):489-95
pubmed: 21296615
Br J Cancer. 2003 Sep 15;89(6):1028-30
pubmed: 12966420
Cell Metab. 2019 Sep 3;30(3):594-606.e3
pubmed: 31257152
Nat Commun. 2022 Jun 15;13(1):3346
pubmed: 35705545
Mamm Genome. 2005 Nov;16(11):829-37
pubmed: 16284798
Cancer Res. 2022 Nov 15;82(22):4179-4190
pubmed: 36066360
Cancer Res. 1991 Dec 15;51(24):6656-9
pubmed: 1742740
Mol Metab. 2020 Nov;41:101046
pubmed: 32599075
Br J Cancer. 2002 Jun 5;86(11):1691-6
pubmed: 12087451
Proteomics. 2015 Sep;15(18):3163-8
pubmed: 25656970
J Mol Biol. 2021 Feb 19;433(4):166788
pubmed: 33387532
Nat Rev Cancer. 2018 Jan;18(1):51-63
pubmed: 29192214
Gastroenterology. 2006 Sep;131(3):900-10
pubmed: 16952558
Hepatology. 2017 Dec;66(6):2055-2065
pubmed: 28777879
Cell. 1998 Mar 6;92(5):645-56
pubmed: 9506519
Mol Cell Proteomics. 2013 Jun;12(6):1709-22
pubmed: 23436904
Cell. 2016 May 5;165(4):896-909
pubmed: 27153497
Cell Metab. 2012 Aug 8;16(2):153-66
pubmed: 22795476
Mol Syst Biol. 2015 Feb 12;11(1):784
pubmed: 25678603
Cancer Res. 2003 Nov 1;63(21):7436-42
pubmed: 14612543
PLoS One. 2015 Mar 19;10(3):e0119888
pubmed: 25789991
Cell Metab. 2015 Jun 2;21(6):805-21
pubmed: 26039447
Nat Protoc. 2009;4(7):1064-72
pubmed: 19561589
JCI Insight. 2020 May 7;5(9):
pubmed: 32298240
Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515
pubmed: 30395287
Br J Cancer. 2022 Aug;127(3):379-382
pubmed: 35523879
Nature. 1970 Sep 12;227(5263):1098-103
pubmed: 5451100
Nutrients. 2018 Sep 01;10(9):
pubmed: 30200408
Anal Chem. 2016 Aug 16;88(16):7899-903
pubmed: 27436111
Clin Cancer Res. 2016 Aug 15;22(16):3999-4004
pubmed: 27340276
Am J Med. 1980 Oct;69(4):491-7
pubmed: 7424938
Nat Rev Cancer. 2014 Nov;14(11):754-62
pubmed: 25291291
Nat Rev Cancer. 2013 Aug;13(8):572-83
pubmed: 23822983
J Nutr Sci Vitaminol (Tokyo). 2016;62(2):81-7
pubmed: 27264091
Cancer Res. 2009 Jun 1;69(11):4918-25
pubmed: 19458066
Blood. 1992 May 1;79(9):2273-80
pubmed: 1571542
EMBO Rep. 2019 Apr;20(4):
pubmed: 30890538
Anal Chem. 2000 Mar 15;72(6):1236-41
pubmed: 10740865
Cancer Treat Rev. 2014 Jul;40(6):685-91
pubmed: 24321611
Genes Dev. 2016 Mar 1;30(5):489-501
pubmed: 26944676
BMJ. 1997 Nov 8;315(7117):1219-22
pubmed: 9393230
J Proteome Res. 2008 Feb;7(2):731-40
pubmed: 18183947
Ann N Y Acad Sci. 1990;585:110-7
pubmed: 2192606
Mol Cell. 2015 Jul 16;59(2):321-32
pubmed: 26073543
Physiol Rev. 2012 Oct;92(4):1515-42
pubmed: 23073625
Diabetes Care. 2010 Jan;33 Suppl 1:S62-9
pubmed: 20042775
J Cachexia Sarcopenia Muscle. 2020 Dec;11(6):1487-1500
pubmed: 33006443
Bioinformatics. 2010 Apr 1;26(7):966-8
pubmed: 20147306
Cell Metab. 2018 May 01;27(5):1067-1080.e5
pubmed: 29685734
BMJ Open Gastroenterol. 2016 Oct 18;3(1):e000097
pubmed: 27843571
Nucleic Acids Res. 2010 Jan;38(Database issue):D750-3
pubmed: 19854939
Anal Chem. 2009 Aug 1;81(15):6165-74
pubmed: 19522513
Physiol Genomics. 2020 May 1;52(5):203-216
pubmed: 32146873
PLoS Comput Biol. 2014 Dec 04;10(12):e1003926
pubmed: 25474468
Cell. 2017 May 4;169(4):651-663.e14
pubmed: 28475894
Cell Metab. 2017 Jan 10;25(1):27-42
pubmed: 27641100
Nature. 2015 Dec 3;528(7580):99-104
pubmed: 26632588
Physiol Rev. 2000 Jul;80(3):1107-213
pubmed: 10893433
Nat Methods. 2015 Nov;12(11):1003-4
pubmed: 26513550
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
J Proteome Res. 2003 Sep-Oct;2(5):488-94
pubmed: 14582645