Abstract
Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites, including glucose 6-phosphate, lactate, 5-phospho-α-D-ribose 1-diphosphate, and serine, via the glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites were required for the survival of cells under low-glucose conditions. Furthermore, activation of thymidine catabolism was observed in human gastric cancer. These findings demonstrate that thymidine can serve as a glycolytic pathway substrate in human cancer cells.
Original language | English |
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Pages (from-to) | 1313-1321 |
Number of pages | 9 |
Journal | Cell Reports |
Volume | 19 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2017 May 16 |
Keywords
- 2-deoxy-D-ribose
- glycolysis
- thymidine
- thymidine catabolism
- thymidine phosphorylase
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)