FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer
Abstract 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...
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doaj-708947fcb7e74b5dbfa6b54733b4fcc32021-01-10T12:37:59ZengBMCCell Communication and Signaling1478-811X2020-01-0118111310.1186/s12964-019-0502-8FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancerWeixing Dai0Xianke Meng1Shaobo Mo2Wenqiang Xiang3Ye Xu4Long Zhang5Renjie Wang6Qingguo Li7Guoxiang Cai8Department of Colorectal Surgery, Fudan University Shanghai Cancer CenterShanghai Jiaotong Univeristy Affiliated Sixth People’s HospitalDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterAbstract 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.https://doi.org/10.1186/s12964-019-0502-8FOXE1HK2GlycolysisCell proliferation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Weixing Dai Xianke Meng Shaobo Mo Wenqiang Xiang Ye Xu Long Zhang Renjie Wang Qingguo Li Guoxiang Cai |
spellingShingle |
Weixing Dai Xianke Meng Shaobo Mo Wenqiang Xiang Ye Xu Long Zhang Renjie Wang Qingguo Li Guoxiang Cai FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer Cell Communication and Signaling FOXE1 HK2 Glycolysis Cell proliferation |
author_facet |
Weixing Dai Xianke Meng Shaobo Mo Wenqiang Xiang Ye Xu Long Zhang Renjie Wang Qingguo Li Guoxiang Cai |
author_sort |
Weixing Dai |
title |
FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer |
title_short |
FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer |
title_full |
FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer |
title_fullStr |
FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer |
title_full_unstemmed |
FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer |
title_sort |
foxe1 represses cell proliferation and warburg effect by inhibiting hk2 in colorectal cancer |
publisher |
BMC |
series |
Cell Communication and Signaling |
issn |
1478-811X |
publishDate |
2020-01-01 |
description |
Abstract 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. |
topic |
FOXE1 HK2 Glycolysis Cell proliferation |
url |
https://doi.org/10.1186/s12964-019-0502-8 |
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