过剩3
mTORC1型
PI3K/AKT/mTOR通路
mTORC2型
厌氧糖酵解
生物
细胞生物学
癌变
癌症研究
细胞生长
葡萄糖转运蛋白
癌细胞
信号转导
生物化学
癌症
内分泌学
遗传学
过剩1
胰岛素
作者
Xiaojun Zha,Zhongdong Hu,Shuang Ji,Fuquan Jin,Keguo Jiang,Chunjia Li,Pan Zhao,Zhenzhen Tu,Xianguo Chen,Lijun Di,Haisheng Zhou,Hongbing Zhang
出处
期刊:Cancer Letters
[Elsevier]
日期:2015-04-01
卷期号:359 (1): 97-106
被引量:45
标识
DOI:10.1016/j.canlet.2015.01.001
摘要
Accumulating evidence indicates that mammalian target of rapamycin (mTOR) exerts a crucial role in aerobic glycolysis and tumorigenesis, but the underlying mechanisms remain largely obscure. Results from Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs) and human cancer cell lines consistently indicate that the expression of glucose transporter 3 (Glut3) is dramatically up-regulated by mTOR. The rapamycin-sensitive mTOR complex 1 (mTORC1), but not the rapamycin-insensitive mTOR complex 2 (mTORC2), was involved in the regulation of Glut3 expression. Moreover, mTORC1 enhances Glut3 expression through the activation of the IKK/NFκB pathway. Depletion of Glut3 led to the suppression of aerobic glycolysis, the inhibition of cell proliferation and colony formation, and the attenuation of the tumorigenic potential of the cells with aberrantly hyper-activated mTORC1 signaling in nude mice. We conclude that Glut3 is a downstream target of mTORC1, and it is critical for oncogenic mTORC1-mediated aerobic glycolysis and tumorigenesis. Hence Glut3 may be a potential target for therapy against cancers caused by the aberrantly activated mTORC1 signaling.
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