Thymidine Catabolism as a Metabolic Strategy for Cancer Survival

Cell Rep. 2017 May 16;19(7):1313-1321. doi: 10.1016/j.celrep.2017.04.061.


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.

Keywords: 2-deoxy-D-ribose; glycolysis; thymidine; thymidine catabolism; thymidine phosphorylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Deoxyribose / pharmacology
  • Glycolysis / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mice
  • Nutritional Status / drug effects
  • Phosphorylation / drug effects
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Thymidine / chemistry
  • Thymidine / metabolism*
  • Thymidine Phosphorylase / metabolism*


  • Deoxyribose
  • Carbon
  • Thymidine Phosphorylase
  • Thymidine