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Thymidine Catabolism as a Metabolic Strategy for Cancer Survival
Sho Tabata1, Masatatsu Yamamoto2, Hisatsugu Goto3
1Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, Japan.
Cell Reports
|May 18, 2017
Summary
Thymidine phosphorylase (TP) enables cancer cells to use thymidine as a carbon source for energy production via the glycolytic pathway, aiding survival during nutrient scarcity. This highlights a novel metabolic vulnerability in tumors.
Area of Science:
- Biochemistry
- Cancer Biology
- Metabolic Pathways
Background:
- Thymidine phosphorylase (TP) is a key enzyme in thymidine metabolism.
- Its role in tumor progression is significant but not fully elucidated.
- Understanding TP's function is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the role of TP-mediated thymidine catabolism in cancer cell survival.
- To identify the metabolic fate of thymidine in TP-expressing cells.
- To determine if thymidine can serve as a substrate in cancer cell metabolism.
Main Methods:
- Enzyme assays to measure thymidine catabolism.
- Metabolomic analysis to identify thymidine-derived products.
- Cell culture under nutrient-deprived conditions (in vitro).
- In vivo studies in relevant cancer models.
Main Results:
- TP-mediated thymidine catabolism supplies carbon for the glycolytic pathway.
- Thymidine is converted to essential metabolites like glucose 6-phosphate and serine.
- These metabolites are vital for cancer cell survival under low-glucose conditions.
- Activated thymidine catabolism was observed in human gastric cancer.
Conclusions:
- Thymidine can serve as a substrate for the glycolytic pathway in human cancer cells.
- TP-mediated thymidine catabolism is a critical survival mechanism for cancer cells.
- Targeting this pathway could offer new therapeutic strategies for cancers exhibiting high TP activity.
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