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2 results on '"Hansen, Thomas Lau Lindestrand"'

1. Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation

Author

Desler, Claus, Durhuus, Jon Ambæk, Hansen, Thomas Lau Lindestrand, Anugula, Sharath, Zelander, Nadia Thaulov, Bøggild, Sisse, Rasmussen, Lene Juel, Desler, Claus, Durhuus, Jon Ambæk, Hansen, Thomas Lau Lindestrand, Anugula, Sharath, Zelander, Nadia Thaulov, Bøggild, Sisse, and Rasmussen, Lene Juel

Abstract

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.

Published
2022

2. Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation.

Author

Desler C, Durhuus JA, Hansen TL, Anugula S, Zelander NT, Bøggild S, and Rasmussen LJ

Subjects
Carcinogenesis, Dihydroorotate Dehydrogenase, Humans, Lysosomes, Pyrimidines, Oxidoreductases Acting on CH-CH Group Donors genetics
Abstract

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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2022
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