Identification of metabolic changes leading to cancer susceptibility in Fanconi anemia cells
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
33316348
DOI
10.1016/j.canlet.2020.12.010
PII: S0304-3835(20)30662-5
Knihovny.cz E-zdroje
- Klíčová slova
- Cancer predisposition, Fanconi anemia, Fumarate, Metabolic reprogramming, Purinosome, de novo purine biosynthesis,
- MeSH
- buněčné linie MeSH
- chromatografie kapalinová MeSH
- Fanconiho anemie metabolismus MeSH
- glykolýza MeSH
- lidé MeSH
- metabolické sítě a dráhy * MeSH
- metabolomika metody MeSH
- oprava DNA MeSH
- oxidativní fosforylace MeSH
- proteomika metody MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Fanconi anemia (FA) is a chromosomal instability disorder of bone marrow associated with aplastic anemia, congenital abnormalities and a high risk of malignancies. The identification of more than two dozen FA genes has revealed a plethora of interacting proteins that are mainly involved in repair of DNA interstrand crosslinks (ICLs). Other important findings associated with FA are inflammation, oxidative stress response, mitochondrial dysfunction and mitophagy. In this work, we performed quantitative proteomic and metabolomic analyses on defective FA cells and identified a number of metabolic abnormalities associated with cancer. In particular, an increased de novo purine biosynthesis, a high concentration of fumarate, and an accumulation of purinosomal clusters were found. This was in parallel with decreased OXPHOS and altered glycolysis. On the whole, our results indicate an association between the need for nitrogenous bases upon impaired DDR in FA cells with a subsequent increase in purine metabolism and a potential role in oncogenesis.
Biosfer Teslab SL Reus Tarragona Spain
CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Chemical Sciences Federico 2 Naples University 1 80126 Naples Italy
Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain
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