Thymidine Catabolism as a Metabolic Strategy for Cancer Survival
Thymidine Catabolism as a Metabolic Strategy for Cancer Survival
复制标题
DOI：
10.1016/j.celrep.2017.04.061
复制
发表时间：
2017-05-16
期刊：
影响因子：
8.8
通讯作者：
Akiyama, Shin-ichi
中科院分区：
文献类型：
--
作者：
Tabata, Sho;Yamamoto, Masatatsu;Akiyama, Shin-ichi
胸苷磷酸化酶（TP）是胸苷催化剂中的限速酶，在肿瘤进展中起着关键作用;然而，这种作用的机制尚未完全了解。在这里，我们发现TP介导的胸苷催化剂可以提供糖酵解途径中的碳源，从而有助于营养剥夺条件下的细胞存活。在TP表达细胞中，胸苷通过体外和体内糖酵解途径转化为代谢产物，包括葡萄糖6-磷酸、乳酸、5-磷酸-α-D-核糖1-二磷酸和丝氨酸。这些胸腺嘧啶衍生的代谢产物是细胞在低葡萄糖条件下存活所必需的。此外，在人胃癌中观察到胸苷催化剂的活化。这些发现表明胸苷可以作为人类癌细胞中糖酵解途径的底物。
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-alpha-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.