Thymidine Catabolism as a Metabolic Strategy for Cancer Survival

Sho Tabata, Masatatsu Yamamoto, Hisatsugu Goto, Akiyoshi Hirayama, Maki Ohishi, Takuya Kuramoto, Atsushi Mitsuhashi, Ryuji Ikeda, Misako Haraguchi, Kohichi Kawahara, Yoshinari Shinsato, Kentaro Minami, Atsuro Saijo, Masaki Hanibuchi, Yasuhiko Nishioka, Saburo Sone, Hiroyasu Esumi, Masaru Tomita, Tomoyoshi Soga, Tatsuhiko FurukawaShin ichi Akiyama

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 languageEnglish
Pages (from-to)1313-1321
Number of pages9
JournalCell Reports
Volume19
Issue number7
DOIs
Publication statusPublished - 2017 May 16

Keywords

  • 2-deoxy-D-ribose
  • glycolysis
  • thymidine
  • thymidine catabolism
  • thymidine phosphorylase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Tabata, S., Yamamoto, M., Goto, H., Hirayama, A., Ohishi, M., Kuramoto, T., Mitsuhashi, A., Ikeda, R., Haraguchi, M., Kawahara, K., Shinsato, Y., Minami, K., Saijo, A., Hanibuchi, M., Nishioka, Y., Sone, S., Esumi, H., Tomita, M., Soga, T., ... Akiyama, S. I. (2017). Thymidine Catabolism as a Metabolic Strategy for Cancer Survival. Cell Reports, 19(7), 1313-1321. https://doi.org/10.1016/j.celrep.2017.04.061