Oncotarget

Research Papers:

FOXM1 promotes reprogramming of glucose metabolism in epithelial ovarian cancer cells via activation of GLUT1 and HK2 transcription

Yu Wang _, Yuyu Yun, Bo Wu, Li Wen, Mingling Wen, Huiling Yang, Lisheng Zhao, Wenchao Liu, Suyun Huang, Ning Wen and Yu Li

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Oncotarget. 2016; 7:47985-47997. https://doi.org/10.18632/oncotarget.10103

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Abstract

Yu Wang1,2,*, Yuyu Yun3,*, Bo Wu3,*, Li Wen2,*, Mingling Wen4, Huiling Yang2, Lisheng Zhao2, Wenchao Liu1, Suyun Huang5,6, Ning Wen2, Yu Li3

1Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China

2Institute of Stomatology, Chinese PLA General Hospital, Beijing, China

3State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi’an, Shaanxi, China

4Department of Pharmacy, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China

5Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

6Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA

*These authors have contributed equally to this work

Correspondence to:

Suyun Huang, email: [email protected]

Ning Wen, email: [email protected]

Yu Li, email: [email protected]

Keywords: FOXM1, GLUT1, HK2, epithelial ovarian cancer, glucose metabolism

Received: December 04, 2015    Accepted: May 12, 2016    Published: June 16, 2016

ABSTRACT

Cancer cells exhibit the reprogrammed metabolism mainly via aerobic glycolysis, a phenomenon known historically as the Warburg effect; however, the underlying mechanisms remain largely unknown. In this study, we characterized the critical role of transcription factor Forkhead box protein M1 (FOXM1) in aerobic glycolysis of human epithelial ovarian cancer (EOC) and its molecular mechanisms. Our data showed that aberrant expression of FOXM1 significantly contributed to the reprogramming of glucose metabolism in EOC cells. Aerobic glycolysis and cell proliferation were down-regulated in EOC cells when FOXM1 gene expression was suppressed by RNA interference. Moreover, knockdown of FOXM1 in EOC cells significantly reduced glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. FOXM1 bound directly to the GLUT1 and HK2 promoter regions and regulated the promoter activities and the expression of the genes at the transcriptional level. This reveals a novel mechanism by which glucose metabolism is regulated by FOXM1. Importantly, we further demonstrated that the expression levels of FOXM1, GLUT1 and HK2 were significantly increased in human EOC tissues relative to normal ovarian tissues, and that FOXM1 expression was positively correlated with GLUT1 and HK2 expression. Taken together, our results show that FOXM1 promotes reprogramming of glucose metabolism in EOC cells via activation of GLUT1 and HK2 transcription, suggesting that FOXM1 may be an important target in aerobic glycolysis pathway for developing novel anticancer agents.


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