The Acidic Brain—Glycolytic Switch in the Microenvironment of Malignant Glioma Article Swipe
Anna Maria Reuss
,
Dominik Groos
,
Michael Buchfelder
,
Nicolai Savaskan
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/ijms22115518
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/ijms22115518
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.
Related Topics
Concepts
Glycolysis
Anaerobic glycolysis
Tumor microenvironment
Glioma
Biology
Warburg effect
Cancer research
Angiogenesis
Cancer cell
Downregulation and upregulation
Tumor progression
Transcription factor
Glucose transporter
Cell biology
Cancer
Metabolism
Biochemistry
Endocrinology
Genetics
Gene
Tumor cells
Insulin
Metadata
- Type
- review
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms22115518
- https://www.mdpi.com/1422-0067/22/11/5518/pdf?version=1621844392
- OA Status
- gold
- Cited By
- 48
- References
- 184
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3164578373
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3164578373Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms22115518Digital Object Identifier
- Title
-
The Acidic Brain—Glycolytic Switch in the Microenvironment of Malignant GliomaWork title
- Type
-
reviewOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-05-24Full publication date if available
- Authors
-
Anna Maria Reuss, Dominik Groos, Michael Buchfelder, Nicolai SavaskanList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms22115518Publisher landing page
- PDF URL
-
https://www.mdpi.com/1422-0067/22/11/5518/pdf?version=1621844392Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/1422-0067/22/11/5518/pdf?version=1621844392Direct OA link when available
- Concepts
-
Glycolysis, Anaerobic glycolysis, Tumor microenvironment, Glioma, Biology, Warburg effect, Cancer research, Angiogenesis, Cancer cell, Downregulation and upregulation, Tumor progression, Transcription factor, Glucose transporter, Cell biology, Cancer, Metabolism, Biochemistry, Endocrinology, Genetics, Gene, Tumor cells, InsulinTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
48Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 12, 2024: 13, 2023: 9, 2022: 11, 2021: 3Per-year citation counts (last 5 years)
- References (count)
-
184Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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