FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer
FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer
复制标题
FOXE1通过抑制结直肠癌中的HK2来抑制细胞增殖和Warburg效应
DOI：
10.1186/s12964-019-0502-8
复制
发表时间：
2020-01-09
影响因子：
8.4
通讯作者：
Cai, Guoxiang
中科院分区：
文献类型：
--
作者：
Dai, Weixing;Meng, Xianke;Cai, Guoxiang
FOXE1是叉头盒（Forkhead box，FOX）转录因子家族的成员，在肿瘤中起重要作用，其低表达导致结直肠癌（colorectal cancer，CRC）患者预后不良。然而，其潜在的机制仍不清楚。材料和方法FOXE 1对结肠癌细胞的生长和糖酵解酶的表达的影响进行了研究在体外和体内。分子生物学实验被用来揭示改变有氧糖酵解的潜在机制。结果FOXE 1在正常结肠组织中的表达明显高于癌组织，FOXE 1的低表达与结直肠癌患者的预后密切相关。在CRC细胞系中沉默FOXE1显著增强细胞增殖和集落形成，并促进葡萄糖消耗和乳酸产生，而FOXE1的强制表达表现出相反的效果。从机制上讲，FOXE 1直接与HK2的启动子区结合，并负调控其转录。结论FOXE 1在大肠癌组织中的表达与HK2的表达呈负相关。
BackgroundLow 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 methodsThe 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.ResultsFOXE1 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.ConclusionFOXE1 functions as a critical tumor suppressor in regulating tumor growth and glycolysis via suppressing HK2 in CRC.