2-Hydroxyglutarate in Cancer Cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00533041" target="_blank" >RIV/67985823:_____/20:00533041 - isvavai.cz</a>
Result on the web
<a href="https://www.liebertpub.com/doi/10.1089/ars.2019.7902" target="_blank" >https://www.liebertpub.com/doi/10.1089/ars.2019.7902</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1089/ars.2019.7902" target="_blank" >10.1089/ars.2019.7902</a>
Alternative languages
Result language
angličtina
Original language name
2-Hydroxyglutarate in Cancer Cells
Original language description
Recent Advances: Both 2-hydroxyglutarate (2HG) enantiomers are associated with reprogrammed metabolism, in grade III/IV glioma, glioblastoma, and acute myeloid leukemia cells, and numerous other cancer types, while acting also in the cross talk of tumors with immune cells. 2HG contributes to specific alternations in cancer metabolism and developed oxidative stress, while also inducing decisions on the differentiation of naive T lymphocytes, and serves as a signal messenger in immune cells. Moreover, 2HG inhibits chromatin-modifying enzymes, namely 2-oxoglutarate-dependent dioxygenases, and interferes with hypoxia-inducible factor (HIF) transcriptome reprogramming and mammalian target of rapamycin (mTOR) pathway, thus dysregulating gene expression and further promoting cancerogenesis. Critical Issues: Typically, heterozygous mutations within the active sites of isocitrate dehydrogenase isoform 1 (IDH1)(R132H) and mitochondrial isocitrate dehydrogenase isoform 2 (IDH2)(R140Q) provide cells with millimolar r-2-hydroxyglutarate (r-2HG) concentrations, whereas side activities of lactate and malate dehydrogenase form submillimolar s-2-hydroxyglutarate (s-2HG). However, even wild-type IDH1 and IDH2, notably under shifts toward reductive carboxylation glutaminolysis or changes in other enzymes, lead to “intermediate” 0.01-0.1 mM 2HG levels, for example, in breast carcinoma compared with 10(-8) M in noncancer cells. Future Directions: Uncovering further molecular metabolism details specific for given cancer cell types and sequence-specific epigenetic alternations will lead to the design of diagnostic approaches, not only for predicting patients' prognosis or uncovering metastases and tumor remissions but also for early diagnostics.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA17-01813S" target="_blank" >GA17-01813S: Redox signaling by mitochondrial reactive oxygen species</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Antioxidants & Redox Signaling
ISSN
1523-0864
e-ISSN
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Volume of the periodical
33
Issue of the periodical within the volume
13
Country of publishing house
US - UNITED STATES
Number of pages
24
Pages from-to
903-926
UT code for WoS article
000508941500001
EID of the result in the Scopus database
2-s2.0-85078258548