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 |
|---|---|
| Pages (from-to) | 1313-1321 |
| Number of pages | 9 |
| Journal | Cell Reports |
| Volume | 19 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2017 May 16 |
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Keywords
- 2-deoxy-D-ribose
- glycolysis
- thymidine
- thymidine catabolism
- thymidine phosphorylase
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Thymidine Catabolism as a Metabolic Strategy for Cancer Survival. / Tabata, Sho; Yamamoto, Masatatsu; Goto, Hisatsugu; Hirayama, Akiyoshi; Ohishi, Maki; Kuramoto, Takuya; Mitsuhashi, Atsushi; Ikeda, Ryuji; Haraguchi, Misako; Kawahara, Kohichi; Shinsato, Yoshinari; Minami, Kentaro; Saijo, Atsuro; Hanibuchi, Masaki; Nishioka, Yasuhiko; Sone, Saburo; Esumi, Hiroyasu; Tomita, Masaru; Soga, Tomoyoshi; Furukawa, Tatsuhiko; Akiyama, Shin ichi.
In: Cell Reports, Vol. 19, No. 7, 16.05.2017, p. 1313-1321.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thymidine Catabolism as a Metabolic Strategy for Cancer Survival
AU - Tabata, Sho
AU - Yamamoto, Masatatsu
AU - Goto, Hisatsugu
AU - Hirayama, Akiyoshi
AU - Ohishi, Maki
AU - Kuramoto, Takuya
AU - Mitsuhashi, Atsushi
AU - Ikeda, Ryuji
AU - Haraguchi, Misako
AU - Kawahara, Kohichi
AU - Shinsato, Yoshinari
AU - Minami, Kentaro
AU - Saijo, Atsuro
AU - Hanibuchi, Masaki
AU - Nishioka, Yasuhiko
AU - Sone, Saburo
AU - Esumi, Hiroyasu
AU - Tomita, Masaru
AU - Soga, Tomoyoshi
AU - Furukawa, Tatsuhiko
AU - Akiyama, Shin ichi
PY - 2017/5/16
Y1 - 2017/5/16
N2 - 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.
AB - 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.
KW - 2-deoxy-D-ribose
KW - glycolysis
KW - thymidine
KW - thymidine catabolism
KW - thymidine phosphorylase
UR - http://www.scopus.com/inward/record.url?scp=85019195391&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019195391&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2017.04.061
DO - 10.1016/j.celrep.2017.04.061
M3 - Article
C2 - 28514652
AN - SCOPUS:85019195391
VL - 19
SP - 1313
EP - 1321
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 7
ER -