Increased Oxidative Phosphorylation Is Required for Stemness Maintenance in Liver Cancer Stem Cells from Hepatocellular Carcinoma Cell Line HCCLM3 Cells

Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poor...

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Veröffentlicht in:International Journal of Molecular Sciences Jg. 21; H. 15; S. 5276
Hauptverfasser: Liu, Ge, Luo, Qing, Li, Hong, Liu, Qiuping, Ju, Yang, Song, Guanbin
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 25.07.2020
MDPI
Schlagworte:
Acids
cancer stem cells
Cancer therapies
Carcinoma, Hepatocellular
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
cell metabolism
Chemotherapy
Dehydrogenases
Energy
Flow cytometry
Glucose
glycolysis
hepatocellular carcinoma
Humans
Kinases
Liver cancer
Liver Neoplasms
Liver Neoplasms - drug therapy
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Metabolism
Mitochondria
Mitochondria, Liver
Mitochondria, Liver - metabolism
Mitochondria, Liver - pathology
Mitochondrial DNA
Neoplastic Stem Cells
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Oxidative Phosphorylation
Phosphorylation
Quinazolinones
Quinazolinones - pharmacology
Stem cells
Studies
cell metabolism
cancer stem cells
hepatocellular carcinoma
oxidative phosphorylation
glycolysis
ISSN:1422-0067, 1661-6596, 1422-0067
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Abstract Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poorly understood. In this study, we compare the metabolic differences between LCSCs and the hepatocellular carcinoma cell line HCCLM3, and explore the relationship between metabolism and LCSC stemness. We found that LCSCs from the hepatocellular carcinoma cell HCCLM3 exhibited more robust glucose metabolism than HCCLM3, including glycolysis, oxidative phosphorylation (OXPHOS), and pyruvate produced by glycolysis entering mitochondria for OXPHOS. Moreover, 2-deoxy-D-glucose (2-DG) enhanced the LCSC stemness by upregulating OXPHOS. In contrast, Mdivi-1 reduced the levels of OXPHOS and weakened the stemness by inhibiting mitochondrial fission. Together, our findings clarify the relationship between energy metabolism and LCSC stemness and may provide theoretical guidance and potential therapeutic approaches for liver cancer.
AbstractList Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poorly understood. In this study, we compare the metabolic differences between LCSCs and the hepatocellular carcinoma cell line HCCLM3, and explore the relationship between metabolism and LCSC stemness. We found that LCSCs from the hepatocellular carcinoma cell HCCLM3 exhibited more robust glucose metabolism than HCCLM3, including glycolysis, oxidative phosphorylation (OXPHOS), and pyruvate produced by glycolysis entering mitochondria for OXPHOS. Moreover, 2-deoxy-D-glucose (2-DG) enhanced the LCSC stemness by upregulating OXPHOS. In contrast, Mdivi-1 reduced the levels of OXPHOS and weakened the stemness by inhibiting mitochondrial fission. Together, our findings clarify the relationship between energy metabolism and LCSC stemness and may provide theoretical guidance and potential therapeutic approaches for liver cancer.Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poorly understood. In this study, we compare the metabolic differences between LCSCs and the hepatocellular carcinoma cell line HCCLM3, and explore the relationship between metabolism and LCSC stemness. We found that LCSCs from the hepatocellular carcinoma cell HCCLM3 exhibited more robust glucose metabolism than HCCLM3, including glycolysis, oxidative phosphorylation (OXPHOS), and pyruvate produced by glycolysis entering mitochondria for OXPHOS. Moreover, 2-deoxy-D-glucose (2-DG) enhanced the LCSC stemness by upregulating OXPHOS. In contrast, Mdivi-1 reduced the levels of OXPHOS and weakened the stemness by inhibiting mitochondrial fission. Together, our findings clarify the relationship between energy metabolism and LCSC stemness and may provide theoretical guidance and potential therapeutic approaches for liver cancer.
Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poorly understood. In this study, we compare the metabolic differences between LCSCs and the hepatocellular carcinoma cell line HCCLM3, and explore the relationship between metabolism and LCSC stemness. We found that LCSCs from the hepatocellular carcinoma cell HCCLM3 exhibited more robust glucose metabolism than HCCLM3, including glycolysis, oxidative phosphorylation (OXPHOS), and pyruvate produced by glycolysis entering mitochondria for OXPHOS. Moreover, 2-deoxy-D-glucose (2-DG) enhanced the LCSC stemness by upregulating OXPHOS. In contrast, Mdivi-1 reduced the levels of OXPHOS and weakened the stemness by inhibiting mitochondrial fission. Together, our findings clarify the relationship between energy metabolism and LCSC stemness and may provide theoretical guidance and potential therapeutic approaches for liver cancer.
Author Ge Liu
Qing Luo
Qiuping Liu
Yang Ju
Hong Li
Guanbin Song
AuthorAffiliation 2 Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan; ju@mech.nagoya-u.ac.jp
1 Key Laboratory of Biorheological Science & Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China; liuge@cqu.edu.cn (G.L.); qing.luo@cqu.edu.cn (Q.L.); li_hong@cqu.edu.cn (H.L.); liuqp@cqu.edu.cn (Q.L.)
AuthorAffiliation_xml – name: 1 Key Laboratory of Biorheological Science & Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China; liuge@cqu.edu.cn (G.L.); qing.luo@cqu.edu.cn (Q.L.); li_hong@cqu.edu.cn (H.L.); liuqp@cqu.edu.cn (Q.L.)
– name: 2 Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan; ju@mech.nagoya-u.ac.jp
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Issue 15
Keywords cell metabolism
cancer stem cells
hepatocellular carcinoma
oxidative phosphorylation
glycolysis
Language English
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Snippet Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely...
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SubjectTerms Acids
cancer stem cells
Cancer therapies
Carcinoma, Hepatocellular
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
cell metabolism
Chemotherapy
Dehydrogenases
Energy
Flow cytometry
Glucose
glycolysis
hepatocellular carcinoma
Humans
Kinases
Liver cancer
Liver Neoplasms
Liver Neoplasms - drug therapy
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Metabolism
Mitochondria
Mitochondria, Liver
Mitochondria, Liver - metabolism
Mitochondria, Liver - pathology
Mitochondrial DNA
Neoplastic Stem Cells
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Oxidative Phosphorylation
Phosphorylation
Quinazolinones
Quinazolinones - pharmacology
Stem cells
Studies
Title Increased Oxidative Phosphorylation Is Required for Stemness Maintenance in Liver Cancer Stem Cells from Hepatocellular Carcinoma Cell Line HCCLM3 Cells
URI https://cir.nii.ac.jp/crid/1872835442589264128
https://www.ncbi.nlm.nih.gov/pubmed/32722385
https://www.proquest.com/docview/2428700825
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https://pubmed.ncbi.nlm.nih.gov/PMC7432880
Volume 21
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