HIF-1-Dependent Reprogramming of Glucose Metabolic Pathway of Cancer Cells and Its Therapeutic Significance

Normal cells produce adenosine 5′-triphosphate (ATP) mainly through mitochondrial oxidative phosphorylation (OXPHOS) when oxygen is available. Most cancer cells, on the other hand, are known to produce energy predominantly through accelerated glycolysis, followed by lactic acid fermentation even und...

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Veröffentlicht in:International journal of molecular sciences Jg. 20; H. 2; S. 238
Hauptverfasser: Nagao, Ayako, Kobayashi, Minoru, Koyasu, Sho, Chow, Christalle C. T., Harada, Hiroshi
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 09.01.2019
MDPI
Schlagworte:
Animals
Cancer
Cellular Reprogramming - genetics
Dehydrogenases
Enzymes
Fermentation
Gene expression
Glucose
Glucose - metabolism
Glycolysis
Humans
Hypoxia
Hypoxia - genetics
Hypoxia - metabolism
Hypoxia-Inducible Factor 1 - genetics
Hypoxia-Inducible Factor 1 - metabolism
Kinases
Metabolic Networks and Pathways
Metabolism
Metabolites
Mitochondria - genetics
Mitochondria - metabolism
Mutation
Oxidative Phosphorylation
Proteins
Radiation Tolerance - genetics
Review
Sulfur
Transcription factors
HIF-1
hypoxia
cancer
glucose metabolism
ISSN:1422-0067, 1661-6596, 1422-0067
Online-Zugang:Volltext
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Zusammenfassung:Normal cells produce adenosine 5′-triphosphate (ATP) mainly through mitochondrial oxidative phosphorylation (OXPHOS) when oxygen is available. Most cancer cells, on the other hand, are known to produce energy predominantly through accelerated glycolysis, followed by lactic acid fermentation even under normoxic conditions. This metabolic phenomenon, known as aerobic glycolysis or the Warburg effect, is less efficient compared with OXPHOS, from the viewpoint of the amount of ATP produced from one molecule of glucose. However, it and its accompanying pathway, the pentose phosphate pathway (PPP), have been reported to provide advantages for cancer cells by producing various metabolites essential for proliferation, malignant progression, and chemo/radioresistance. Here, focusing on a master transcriptional regulator of adaptive responses to hypoxia, the hypoxia-inducible factor 1 (HIF-1), we review the accumulated knowledge on the molecular basis and functions of the Warburg effect and its accompanying pathways. In addition, we summarize our own findings revealing that a novel HIF-1-activating factor enhances the antioxidant capacity and resultant radioresistance of cancer cells though reprogramming of the glucose metabolic pathway.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20020238