FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer

被引：36
作者：
Dai, Weixing [1 ,2 ]
Meng, Xianke [3 ]
Mo, Shaobo [1 ,2 ]
Xiang, Wenqiang [1 ,2 ]
Xu, Ye [1 ,2 ]
Zhang, Long [1 ,4 ]
Wang, Renjie [1 ,2 ]
Li, Qingguo [1 ,2 ]
Cai, Guoxiang [1 ,2 ]
机构：
[1] Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, 270 Dongan Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, 270 Dongan Rd, Shanghai 200032, Peoples R China
[3] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China
[4] Fudan Univ, Canc Inst, Shanghai Canc Ctr, Shanghai 200032, Peoples R China
来源：
CELL COMMUNICATION AND SIGNALING | 2020年 / 18卷 / 01期
基金：
中国国家自然科学基金;
关键词：
FOXE1; HK2; Glycolysis; Cell proliferation; EPITHELIAL-MESENCHYMAL TRANSITION; ENERGY-METABOLISM; POOR-PROGNOSIS; FOXM1; PROMOTES; GLYCOLYSIS; PROGRESSION; HEXOKINASE; HALLMARK;
D O I：
10.1186/s12964-019-0502-8
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Background Low expression of FOXE1, a member of Forkhead box (FOX) transcription factor family that plays vital roles in cancers, contributes to poor prognosis of colorectal cancer (CRC) patients. However, the underlying mechanism remains unclear. Materials and methods The effects of FOXE1 on the growth of colon cancer cells and the expression of glycolytic enzymes were investigated in vitro and in vivo. Molecular biological experiments were used to reveal the underlying mechanisms of altered aerobic glycolysis. CRC tissue specimens were used to determine the clinical association of ectopic metabolism caused by dysregulated FOXE1. Results FOXE1 is highly expressed in normal colon tissues compared with cancer tissues and low expression of FOXE1 is significantly associated with poor prognosis of CRC patients. Silencing FOXE1 in CRC cell lines dramatically enhanced cell proliferation and colony formation and promoted glucose consumption and lactate production, while enforced expression of FOXE1 manifested the opposite effects. Mechanistically, FOXE1 bound directly to the promoter region of HK2 and negatively regulated its transcription. Furthermore, the expression of FOXE1 in CRC tissues was negatively correlated with that of HK2. Conclusion FOXE1 functions as a critical tumor suppressor in regulating tumor growth and glycolysis via suppressing HK2 in CRC.
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页数：13
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