癌细胞
糖酵解
苹果酸酶
磷酸戊糖途径
烟酰胺腺嘌呤二核苷酸磷酸
生物化学
酶
化学
细胞生长
细胞生物学
癌症
生物
脱氢酶
氧化酶试验
遗传学
作者
Shunji Murai,Ayumi Ando,Shunsuke Ebara,Megumi Hirayama,Yoshinori Satomi,Takahito Hara
出处
期刊:Oncogenesis
[Springer Nature]
日期:2017-05-08
卷期号:6 (5): e329-e329
被引量:54
标识
DOI:10.1038/oncsis.2017.34
摘要
Malic enzyme 1 (ME1) regulates one of the main pathways that provide nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for cancer cell growth through maintenance of redox balance and biosynthesis processes in the cytoplasm. In this study, we found that ME1 inhibition disrupted metabolism in cancer cells and inhibited cancer cell growth by inducing senescence or apoptosis. In glucose-restricted culture conditions, cancer cells increased ME1 expression, and tracer experiments with labelled glutamine revealed that the flux of ME1-derived pyruvate to citrate was enhanced. In addition, cancer cells showed higher sensitivity to ME1 depletion in glucose-restricted conditions compared to normal culture conditions. These results suggest that in a low-glucose environment, where glycolysis and the pentose phosphate pathway (PPP) is attenuated, cancer cells become dependent on ME1 for the supply of NADPH and pyruvate. Our data demonstrate that ME1 is a promising target for cancer treatment, and a strategy using ME1 inhibitors combined with inhibition of glycolysis, PPP or redox balance regulators may provide an effective therapeutic option.
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