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Region Hovedstaden - en del af Københavns Universitetshospital
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Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation

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The correlation between mitochondrial function and oncogenesis is complex and is not fully understood. Here we determine the importance of mitochondrial-linked pyrimidine synthesis for the aggressiveness of cancer cells. The enzyme dihydroorotate dehydrogenase (DHODH) links oxidative phosphorylation to de novo synthesis of pyrimidines. We demonstrate that an inhibition of DHODH results in a respiration-independent significant increase of anchorage-independent growth but does not affect DNA repair ability. Instead, we show an autophagy-independent increase of lysosomes. The results of this study suggest that inhibition of mitochondrial-linked pyrimidine synthesis in cancer cells results in a more aggressive tumor phenotype.

OriginalsprogEngelsk
TidsskriftMitochondrion
Vol/bind64
Sider (fra-til)73-81
Antal sider9
ISSN1567-7249
DOI
StatusUdgivet - maj 2022

Bibliografisk note

Copyright © 2022. Published by Elsevier B.V.

ID: 75961598