Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme

• DOI: 10.1084/jem.20101470
• Publication Date: 2011-01-18T03:59:15Z
• Authors: Amparo Wolf; Sameer Agnihotri; Johann Micallef; Joydeep Mukherjee; Nesrin Sabha; Rob Cairns; Cynthia Hawkins; Abhijit Guha
• Keywords: Warburg Effect; Anaerobic glycolysis; Hexokinase; PKM2; Temozolomide

Proliferating embryonic and cancer cells preferentially use aerobic glycolysis to support growth, a metabolic alteration commonly referred as the “Warburg effect.” Here, we show that glycolytic enzyme hexokinase 2 (HK2) is crucial for Warburg effect in human glioblastoma multiforme (GBM), most common malignant brain tumor. In contrast normal low-grade gliomas, which express predominantly HK1, GBMs increased HK2 expression. expression correlates with worse overall survival of GBM patients. Depletion HK2, but neither HK1 nor pyruvate kinase M2, restored oxidative glucose metabolism sensitivity cell death inducers such radiation temozolomide. Intracranial xenografts HK2-depleted showed decreased proliferation angiogenesis, invasion, well diminished hypoxia inducible factor 1α vascular endothelial growth factor. contrast, exogenous led proliferation, therapeutic resistance, intracranial growth. Growth was dependent on both phosphorylation mitochondrial translocation mediated by AKT signaling, often aberrantly activated GBMs. Collectively, these findings suggest strategies modulate effect, targeting may interfere some