Cancer stem cell molecular reprogramming of the Warburg effect in glioblastomas: a new target gleaned from an old concept
| Autor: | Andrew J. Tsung, Carlen A Yuen, Maheedhara R. Guda, Swapna Asuthkar, Kiran Kumar Velpula |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Angiogenesis Inhibitors Oxidative phosphorylation Review PKM2 Biology Oxidative Phosphorylation 03 medical and health sciences Cancer stem cell medicine Basic Helix-Loop-Helix Transcription Factors Humans Glycolysis Molecular Targeted Therapy Cell Self Renewal Transcription factor Dichloroacetic Acid Brain Neoplasms General Medicine Cellular Reprogramming Warburg effect Cell Hypoxia Neoplasm Proteins Up-Regulation 030104 developmental biology medicine.anatomical_structure Drug Resistance Neoplasm Cancer research Neoplastic Stem Cells Glioblastoma Reprogramming Signal Transduction |
| Popis: | Prior targeted treatment for glioblastoma multiforme (GBM) with anti-angiogenic agents, such as bevacizumab, has been met with limited success potentially owing to GBM tumor's ability to develop a hypoxia-induced escape mechanism – a glycolytic switch from oxidative phosphorylation to glycolysis, an old concept known as the Warburg effect. New studies points to a subpopulation of cells as a source for treatment-resistance, cancer stem cells (CSCs). Taken together, the induction of the Warburg effect leads to the promotion of CSC self-renewal and undifferentiation. In response to hypoxia, hypoxia-inducible transcription factor is upregulated and is the central driver in setting off the cascade of events in CSC metabolic reprogramming. Hypoxia-inducible transcription factor upregulates GLUT1 to increase glucose uptake into the cell, upregulates HK2 and PK during glycolysis, upregulates LDHA in the termination of glycolysis, and downregulates PDH to redirect energy production toward glycolysis. This review aims to unite these old and new concepts simultaneously and examine potential enzyme targets driven by hypoxia in the glycolytic phenotype of CSCs to reverse the metabolic shift induced by the Warburg effect. |
| Databáze: | OpenAIRE |
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