Klotho negatively regulated aerobic glycolysis in colorectal cancer via ERK/HIF1α axis
Abstract Background Klotho (KL) was originally characterized as an aging suppressor gene, and has been identified as a tumor suppressor gene in a variety of cancers, including colorectal cancer. Recent years have witnessed the importance of metabolism transformation in cancer cell malignancies maint...
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doaj-665670dda6514392ad8029887da087312020-11-25T02:01:48ZengBMCCell Communication and Signaling1478-811X2018-06-0116111110.1186/s12964-018-0241-2Klotho negatively regulated aerobic glycolysis in colorectal cancer via ERK/HIF1α axisQingguo Li0Yaqi Li1Lei Liang2Jing Li3Dakui Luo4Qi Liu5Sanjun Cai6Xinxiang Li7Department of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartments of CyberKnife, Huashan Hospital, Fudan UniversityDepartment 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 Klotho (KL) was originally characterized as an aging suppressor gene, and has been identified as a tumor suppressor gene in a variety of cancers, including colorectal cancer. Recent years have witnessed the importance of metabolism transformation in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. Our previous studies demonstrated that KL played negative roles in colon cancer cell proliferation and metastasis. However, its role in the cancer cell reprogramming has seldom been reported. The aim of this study was to examine the role of KL in aerobic glycolysis in colorectal cancer. Methods Combining maximum standardized uptake value (SUVmax), which was obtained preoperatively via a PET/CT scan, with immunohistochemistry staining, we analyzed the correlation between SUVmax and KL expression in colorectal cancer tissues. The impact of KL on glucose metabolism and its mechanisms were further validated in vitro and in vivo. Results Patients with lower KL expression exhibited higher 18F-FDG uptake (P < 0.05), indicating that KL might participate in aerobic glycolysis regulation. In vitro assay by using colon cancer cell lines further supported this observation. By overexpressing KL in HTC116 and SW480 cells, we observed that the glycolysis was inhibited and the mitochondrial respiration increased, indicating that KL was a negative regulator of aerobic glycolysis. To seek for the underlying mechanisms, we tried to dig out the relation between KL and HIF1α signaling pathway, and found that KL negatively regulated HIF1α protein level and transcriptional activity. Western blot analysis showed that KL overexpression negatively regulated ERK pathway, and KL regulated aerobic glycolysis in part through its regulation of ERK/ HIF1α axis. Conclusions Taken together, KL is a negative regulator of aerobic glycolysis and KL inhibited glucose metabolism transformation via the ERK/ HIF1α axis.http://link.springer.com/article/10.1186/s12964-018-0241-2Colorectal cancerKlothoAerobic glycolysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qingguo Li Yaqi Li Lei Liang Jing Li Dakui Luo Qi Liu Sanjun Cai Xinxiang Li |
spellingShingle |
Qingguo Li Yaqi Li Lei Liang Jing Li Dakui Luo Qi Liu Sanjun Cai Xinxiang Li Klotho negatively regulated aerobic glycolysis in colorectal cancer via ERK/HIF1α axis Cell Communication and Signaling Colorectal cancer Klotho Aerobic glycolysis |
author_facet |
Qingguo Li Yaqi Li Lei Liang Jing Li Dakui Luo Qi Liu Sanjun Cai Xinxiang Li |
author_sort |
Qingguo Li |
title |
Klotho negatively regulated aerobic glycolysis in colorectal cancer via ERK/HIF1α axis |
title_short |
Klotho negatively regulated aerobic glycolysis in colorectal cancer via ERK/HIF1α axis |
title_full |
Klotho negatively regulated aerobic glycolysis in colorectal cancer via ERK/HIF1α axis |
title_fullStr |
Klotho negatively regulated aerobic glycolysis in colorectal cancer via ERK/HIF1α axis |
title_full_unstemmed |
Klotho negatively regulated aerobic glycolysis in colorectal cancer via ERK/HIF1α axis |
title_sort |
klotho negatively regulated aerobic glycolysis in colorectal cancer via erk/hif1α axis |
publisher |
BMC |
series |
Cell Communication and Signaling |
issn |
1478-811X |
publishDate |
2018-06-01 |
description |
Abstract Background Klotho (KL) was originally characterized as an aging suppressor gene, and has been identified as a tumor suppressor gene in a variety of cancers, including colorectal cancer. Recent years have witnessed the importance of metabolism transformation in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. Our previous studies demonstrated that KL played negative roles in colon cancer cell proliferation and metastasis. However, its role in the cancer cell reprogramming has seldom been reported. The aim of this study was to examine the role of KL in aerobic glycolysis in colorectal cancer. Methods Combining maximum standardized uptake value (SUVmax), which was obtained preoperatively via a PET/CT scan, with immunohistochemistry staining, we analyzed the correlation between SUVmax and KL expression in colorectal cancer tissues. The impact of KL on glucose metabolism and its mechanisms were further validated in vitro and in vivo. Results Patients with lower KL expression exhibited higher 18F-FDG uptake (P < 0.05), indicating that KL might participate in aerobic glycolysis regulation. In vitro assay by using colon cancer cell lines further supported this observation. By overexpressing KL in HTC116 and SW480 cells, we observed that the glycolysis was inhibited and the mitochondrial respiration increased, indicating that KL was a negative regulator of aerobic glycolysis. To seek for the underlying mechanisms, we tried to dig out the relation between KL and HIF1α signaling pathway, and found that KL negatively regulated HIF1α protein level and transcriptional activity. Western blot analysis showed that KL overexpression negatively regulated ERK pathway, and KL regulated aerobic glycolysis in part through its regulation of ERK/ HIF1α axis. Conclusions Taken together, KL is a negative regulator of aerobic glycolysis and KL inhibited glucose metabolism transformation via the ERK/ HIF1α axis. |
topic |
Colorectal cancer Klotho Aerobic glycolysis |
url |
http://link.springer.com/article/10.1186/s12964-018-0241-2 |
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