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Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions

Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic ana...

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Autores principales: Lin, Shu-Hai, Liu, Tengfei, Ming, Xiaoyan, Tang, Zhi, Fu, Li, Schmitt-Kopplin, Philippe, Kanawati, Basem, Guan, Xin-Yuan, Cai, Zongwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754761/
https://www.ncbi.nlm.nih.gov/pubmed/26878908
http://dx.doi.org/10.1038/srep21184
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author Lin, Shu-Hai
Liu, Tengfei
Ming, Xiaoyan
Tang, Zhi
Fu, Li
Schmitt-Kopplin, Philippe
Kanawati, Basem
Guan, Xin-Yuan
Cai, Zongwei
author_facet Lin, Shu-Hai
Liu, Tengfei
Ming, Xiaoyan
Tang, Zhi
Fu, Li
Schmitt-Kopplin, Philippe
Kanawati, Basem
Guan, Xin-Yuan
Cai, Zongwei
author_sort Lin, Shu-Hai
collection PubMed
description Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic analysis profiled cellular metabolome in CSCs of hepatocellular carcinoma using CD133 cell-surface marker. The metabolic signatures of CD133-positive subpopulation compared to CD133-negative cells highlighted HBP as one of the distinct metabolic pathways, prompting us to uncover the role of HBP in maintenance of CSC-like phenotype. To address this, CSC-like phenotypes and cell survival were investigated in cancer cells under low glucose conditions. As a result, HBP inhibitor azaserine reduced CD133-positive subpopulation and CD133 expression under high glucose condition. Furthermore, treatment of N-Acetylglucosamine in part restores CD133-positive subpopulation when either 2.5 mM glucose in culture media or glycolytic inhibitor 2-deoxy-D-glucose in HCC cell lines was applied, enhancing CD133 expression as well as promoting cancer cell survival. Together, HBP might be a key metabolic determinant in the functions of hepatic CSC marker CD133.
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spelling pubmed-47547612016-02-24 Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions Lin, Shu-Hai Liu, Tengfei Ming, Xiaoyan Tang, Zhi Fu, Li Schmitt-Kopplin, Philippe Kanawati, Basem Guan, Xin-Yuan Cai, Zongwei Sci Rep Article Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic analysis profiled cellular metabolome in CSCs of hepatocellular carcinoma using CD133 cell-surface marker. The metabolic signatures of CD133-positive subpopulation compared to CD133-negative cells highlighted HBP as one of the distinct metabolic pathways, prompting us to uncover the role of HBP in maintenance of CSC-like phenotype. To address this, CSC-like phenotypes and cell survival were investigated in cancer cells under low glucose conditions. As a result, HBP inhibitor azaserine reduced CD133-positive subpopulation and CD133 expression under high glucose condition. Furthermore, treatment of N-Acetylglucosamine in part restores CD133-positive subpopulation when either 2.5 mM glucose in culture media or glycolytic inhibitor 2-deoxy-D-glucose in HCC cell lines was applied, enhancing CD133 expression as well as promoting cancer cell survival. Together, HBP might be a key metabolic determinant in the functions of hepatic CSC marker CD133. Nature Publishing Group 2016-02-16 /pmc/articles/PMC4754761/ /pubmed/26878908 http://dx.doi.org/10.1038/srep21184 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lin, Shu-Hai
Liu, Tengfei
Ming, Xiaoyan
Tang, Zhi
Fu, Li
Schmitt-Kopplin, Philippe
Kanawati, Basem
Guan, Xin-Yuan
Cai, Zongwei
Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions
title Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions
title_full Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions
title_fullStr Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions
title_full_unstemmed Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions
title_short Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions
title_sort regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker cd133 under low glucose conditions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754761/
https://www.ncbi.nlm.nih.gov/pubmed/26878908
http://dx.doi.org/10.1038/srep21184
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