期刊
FRONTIERS IN ONCOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.583217
关键词
pyruvate dehydrogenase kinase; tricarboxylic acid cycle; oxidative phosphorylation; Warburg effect; aerobic glycolysis; prostate cancer; cancer metabolism; therapy resistance
类别
资金
- Austrian Science Fund (FWF): IPPTO project [DOC 59-B33]
- COMET Competence Center CBmed-Center for Biomarker Research in Medicine [FA791A0906]
- Austrian Federal Ministry for Transport, Innovation and Technology (BMVIT)
- Austrian Federal Ministry for Digital and Economic Affairs (BMDW)
- Land Steiermark (Department 12, Business and Innovation)
- Styrian Business Promotion Agency (SFG)
- Vienna Business Agency
- FWF [P26011]
- Christian Doppler Lab for Applied Metabolomics
- Austrian Federal Ministry for Transport, Innovation and Technology
- National Foundation for Research, Technology and Development
A metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis-known as the Warburg effect-is characteristic for many cancers. It gives the cancer cells a survival advantage in the hypoxic tumor microenvironment and protects them from cytotoxic effects of oxidative damage and apoptosis. The main regulators of this metabolic shift are the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinase (PDK) isoforms 1-4. PDK is known to be overexpressed in several cancers and is associated with bad prognosis and therapy resistance. Whereas the expression of PDK1-3 is tissue specific, PDK4 expression is dependent on the energetic state of the whole organism. In contrast to other PDK isoforms, not only oncogenic, but also tumor suppressive functions of PDK4 have been reported. In tumors that profit from high OXPHOS and high de novo fatty acid synthesis, PDK4 can have a protective effect. This is the case for prostate cancer, the most common cancer in men, and makes PDK4 an interesting therapeutic target. While most work is focused on PDK in tumors characterized by high glycolytic activity, little research is devoted to those cases where PDK4 acts protective and is therefore highly needed.
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