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
Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, Japan.
Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
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.
胸苷磷酸化酶（TP）是胸苷分解代谢中的一种限速酶，在肿瘤进展中起关键作用；然而，这一作用背后的机制尚未完全明确。在此，我们发现TP介导的胸苷分解代谢能够为糖酵解途径提供碳源，从而在营养剥夺条件下有助于细胞存活。在表达TP的细胞中，胸苷在体外和体内均通过糖酵解途径转化为代谢产物，包括6-磷酸葡萄糖、乳酸、5-磷酸-α-D-核糖-1-二磷酸和丝氨酸。这些源自胸苷的代谢产物是低葡萄糖条件下细胞存活所必需的。此外，在人类胃癌中观察到了胸苷分解代谢的激活。这些发现表明，胸苷可作为人类癌细胞中糖酵解途径的底物。
