Cell metabolism, 2012-12, Vol.16 (6), p.751-764
2012
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- Autor(en) / Beteiligte
- Titel
- Glucose Utilization via Glycogen Phosphorylase Sustains Proliferation and Prevents Premature Senescence in Cancer Cells
- Ist Teil von
- Cell metabolism, 2012-12, Vol.16 (6), p.751-764
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Metabolic reprogramming of cancer cells provides energy and multiple intermediates critical for cell growth. Hypoxia in tumors represents a hostile environment that can encourage these transformations. We report that glycogen metabolism is upregulated in tumors in vivo and in cancer cells in vitro in response to hypoxia. In vitro, hypoxia induced an early accumulation of glycogen, followed by a gradual decline. Concordantly, glycogen synthase (GYS1) showed a rapid induction, followed by a later increase of glycogen phosphorylase (PYGL). PYGL depletion and the consequent glycogen accumulation led to increased reactive oxygen species (ROS) levels that contributed to a p53-dependent induction of senescence and markedly impaired tumorigenesis in vivo. Metabolic analyses indicated that glycogen degradation by PYGL is important for the optimal function of the pentose phosphate pathway. Thus, glycogen metabolism is a key pathway induced by hypoxia, necessary for optimal glucose utilization, which represents a targetable mechanism of metabolic adaptation. [Display omitted] ► Glycogen metabolism is upregulated by hypoxia in cancer cells in vitro and in vivo ► Synthesis versus degradation enzymes have a marked difference in temporal induction ► Metabolism of glucose via glycogen sustains the pentose phosphate pathway ► Depletion of PYGL induces senescence and inhibits tumor growth
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1550-4131eISSN: 1932-7420DOI: 10.1016/j.cmet.2012.10.017Titel-ID: cdi_proquest_miscellaneous_1237090664
- Format
- –
- Schlagworte
- Angiogenesis Inhibitors - pharmacology, Animals, Antibodies, Monoclonal, Humanized - pharmacology, Bevacizumab, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Cell Hypoxia - drug effects, Cell Line, Tumor, Cell Proliferation - drug effects, Cellular Senescence - drug effects, Female, Glucose - pharmacology, Glycogen - metabolism, Glycogen Phosphorylase - antagonists & inhibitors, Glycogen Phosphorylase - genetics, Glycogen Phosphorylase - metabolism, Glycogen Synthase - metabolism, HCT116 Cells, Humans, MCF-7 Cells, Mice, Mice, Nude, Reactive Oxygen Species - metabolism, RNA Interference, RNA, Small Interfering - metabolism, Transplantation, Heterologous, Tumor Suppressor Protein p53 - metabolism