Thymidine Catabolism as a Metabolic Strategy for Cancer Survival
2017
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 Furukawa | Shin-ichi Akiyama
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.
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