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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)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Hepatocellular-carcinoma; Stem/progenitor Cells; Metabolic Pathways; Initiating Cells; Identification; Growth; Activation; Survival
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 6, Heft: , Seiten: , Artikelnummer: 21184 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit BioGeoChemistry and Analytics (BGC)