CUE domain-containing protein 2 promotes the Warburg effect and tumorigenesis.
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 (CUE domain-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 14-3-3ζ, 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.
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Xiuying
X
Zhong
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Shengya
S
Tian
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Xiang
X
Zhang
Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China.
Xinwei
X
Diao
Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China.
Fangting
F
Dong
Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China.
Jie
J
Yang
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Zhaoyong
Z
Li
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Linchong
L
Sun
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Lin
L
Wang
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Xiaoping
X
He
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Gongwei
G
Wu
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Xin
X
Hu
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Lihua
L
Wang
State Key Laboratory of Oncology in Southern China and Departments of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.
Libing
L
Song
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Huafeng
0000-0001-9923-7531
H
Zhang
Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China.
Xin
X
Pan
Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China liailing@hotmail.com pgao2@ustc.edu.cn.
Ailing
A
Li
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China liailing@hotmail.com pgao2@ustc.edu.cn.
Ping
0000-0002-6930-7989
P
Gao
D048948:14-3-3 Proteins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D063646:Carcinogenesis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D046888:Tissue Array Analysis; D015533:Transcriptional Activation; D015854:Up-Regulation
D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; C519556:CUEDC2 protein, human; D002352:Carrier Proteins; D051274:Glucose Transporter Type 3; D007527:Isoenzymes; D008565:Membrane Proteins; D011965:Receptors, Glucocorticoid; C495687:SLC2A3 protein, human; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5

LDHA
; CUEDC2; GLUT3; Warburg effect; tumorigenesis