The Acidic Brain—Glycolytic Switch in the Microenvironment of Malignant Glioma
| Autor: | Dominik Groos, Anna Maria Reuss, Michael Buchfelder, Nicolai E. Savaskan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Angiogenic Switch
QH301-705.5 Angiogenesis MCT4 Review MCT1 Catalysis Inorganic Chemistry angiogenesis Downregulation and upregulation glioma Glioma medicine HIF Animals Humans tumor microenvironment Lactic Acid ddc:610 Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Transcription factor Spectroscopy Carbonic Anhydrases Brain Chemistry acidic lactate Tumor microenvironment Neovascularization Pathologic Brain Neoplasms Chemistry Organic Chemistry Brain General Medicine Hydrogen-Ion Concentration medicine.disease Computer Science Applications Anaerobic glycolysis Cancer cell Cancer research glycolytic Glycolysis carbonic anhydrase (CA)IX |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 5518, p 5518 (2021) International Journal of Molecular Sciences |
| Popis: | Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct tumor zones of this heterogeneous neoplasm develop their own microenvironment, in which subpopulations of cancer cells communicate. Adaptation to hypoxia in the center of the expanding tumor mass leads to the glycolytic and angiogenic switch, accompanied by upregulation of different glycolytic enzymes, transporters, and other metabolites. These processes render the tumor microenvironment more acidic, remodel the extracellular matrix, and create energy gradients for the metabolic communication between different cancer cells in distinct tumor zones. Escape mechanisms from hypoxia-induced cell death and energy deprivation are the result. The functional consequences are more aggressive and malignant behavior with enhanced proliferation and survival, migration and invasiveness, and the induction of angiogenesis. In this review, we go from the biochemical principles of aerobic and anaerobic glycolysis over the glycolytic switch, regulated by the key transcription factor hypoxia-inducible factor (HIF)-1α, to other important metabolic players like the monocarboxylate transporters (MCTs)1 and 4. We discuss the metabolic symbiosis model via lactate shuttling in the acidic tumor microenvironment and highlight the functional consequences of the glycolytic switch on glioma malignancy. Furthermore, we illustrate regulation by micro ribonucleic acids (miRNAs) and the connection between isocitrate dehydrogenase (IDH) mutation status and glycolytic metabolism. Finally, we give an outlook about the diagnostic and therapeutic implications of the glycolytic switch and the relation to tumor immunity in malignant glioma. |
| Databáze: | OpenAIRE |
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