期刊
EMBO REPORTS
卷 18, 期 5, 页码 809-825出版社
WILEY
DOI: 10.15252/embr.201643617
关键词
CUEDC2; GLUT3; LDHA; tumorigenesis; Warburg effect
资金
- National Basic Key Research Program of China [2014CB910600]
- National Natural Science Foundation of China [81530076, 81525022, 31371429, 31571472, 81372148]
- Chinese Academy of Sciences [XDA01010404]
- Fundamental Research Funds for the Central Universities
- Development Foundation of Hefei Center for Physical Science and Technology
- CAS Key Laboratory of Innate Immunity and Chronic Disease
Cancer progression depends on cellular metabolic reprogramming as both direct and indirect consequence of oncogenic lesions; however, the underlying mechanisms are still poorly understood. Here, we report that CUEDC2 ( CUEdomain-containing protein 2) plays a vital role in facilitating aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we show that CUEDC2 upregulates the two key glycolytic proteins GLUT3 and LDHA via interacting with the glucocorticoid receptor (GR) or 14-3-3 zeta, respectively. We further demonstrate that enhanced aerobic glycolysis is essential for the role of CUEDC2 to drive cancer progression. Moreover, using tissue microarray analysis, we show a correlation between the aberrant expression of CUEDC2, and GLUT3 and LDHA in clinical HCC samples, further demonstrating a link between CUEDC2 and the Warburg effect during cancer development. Taken together, our findings reveal a previously unappreciated function of CUEDC2 in cancer cell metabolism and tumorigenesis, illustrating how close oncogenic lesions are intertwined with metabolic alterations promoting cancer progression.
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