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Lin, S.H.* ; Liu, T.* ; Ming, X.* ; Tang, Z.* ; Fu, L.* ; Schmitt-Kopplin, P. ; Kanawati, B. ; Guan, X.Y.* ; Cai, Z.*

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

Sci. Rep. 6:21184 (2016)
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Open Access Gold
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Hepatocellular-carcinoma; Stem/progenitor Cells; Metabolic Pathways; Initiating Cells; Identification; Growth; Activation; Survival
Language
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Quellenangaben Volume: 6, Issue: , Pages: , Article Number: 21184 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
POF-Topic(s) 30202 - Environmental Health
Research field(s) Environmental Sciences
PSP Element(s) G-504800-001
Scopus ID 84958260943
Erfassungsdatum 2016-03-02