期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 456, 期 1, 页码 452-458出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2014.11.105
关键词
Glucose; Glutamine; GIS1; Prostate cancer; TXNIP; GLUT1
资金
- National Natural Science Foundation of China [81272812]
Cancer cells reprogram their metabolism towards aerobic glycolysis and elevated glutaminolysis, which contributes to the aggressive phenotype. Understanding how these metabolic pathways are regulated may provide critical targets for therapeutic intervention. Glutaminase (GLS1) is a key enzyme that converts glutamine to glutamate. In this study, we show the loss of GLS1 function by RNA interference or inhibitor diminished the rates of glucose utilization, growth and invasiveness of prostate cancer cells. We propose that GLS1 positively regulates glucose uptake in addition to glutaminolysis. Further, GLS1 involves the transcriptional repression of thioredoxin interacting protein (T(NIP), which is a potent negative regulator of glucose uptake and aerobic glycolysis. Most importantly, we provided direct evidence that elevated GLS1 expression was highly correlated with the tumor stage and progression in prostate cancer patients. Together, we defined a key role for GLS1 in coupling glutaminolysis of the TCA cycle with elevated glucose uptake and consequently the growth of prostate cancer cells. These data extends the role of GLS1 in regulating cell metabolism and the clinical utility of GLS1 inhibitors in the restriction of essential nutrients. (C) 2014 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据