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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Endocrinol+(Lausanne)
2018 ; 9
(ä): 177
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Deoxyribonucleotide Triphosphate Metabolism in Cancer and Metabolic Disease
#MMPMID29720963
Buj R
; Aird KM
Front Endocrinol (Lausanne)
2018[]; 9
(ä): 177
PMID29720963
show ga
The maintenance of a healthy deoxyribonucleotide triphosphate (dNTP) pool is
critical for the proper replication and repair of both nuclear and mitochondrial
DNA. Temporal, spatial, and ratio imbalances of the four dNTPs have been shown to
have a mutagenic and cytotoxic effect. It is, therefore, essential for cell
homeostasis to maintain the balance between the processes of dNTP biosynthesis
and degradation. Multiple oncogenic signaling pathways, such as c-Myc, p53, and
mTORC1 feed into dNTP metabolism, and there is a clear role for dNTP imbalances
in cancer initiation and progression. Additionally, multiple chemotherapeutics
target these pathways to inhibit nucleotide synthesis. Less is understood about
the role for dNTP levels in metabolic disorders and syndromes and whether
alterations in dNTP levels change cancer incidence in these patients. For
instance, while deficiencies in some metabolic pathways known to play a role in
nucleotide synthesis are pro-tumorigenic (e.g., p53 mutations), others confer an
advantage against the onset of cancer (G6PD). More recent evidence indicates that
there are changes in nucleotide metabolism in diabetes, obesity, and insulin
resistance; however, whether these changes play a mechanistic role is unclear. In
this review, we will address the complex network of metabolic pathways, whereby
cells can fuel dNTP biosynthesis and catabolism in cancer, and we will discuss
the potential role for this pathway in metabolic disease.