Abstract
Cancer is a disorder of cell growth and proliferation, characterized by different metabolic pathways within normal cells. The Warburg effect is a major metabolic process in cancer cells that affects the cellular responses, such as proliferation and apoptosis. Various signaling factors down/upregulate factors of the glycolysis pathway in cancer cells, and these signaling factors are ubiquitinated/deubiquitinated via the ubiquitin–proteasome system (UPS). Depending on the target protein, DUBs act as both an oncoprotein and a tumor suppressor. Since the degradation of tumor suppressors and stabilization of oncoproteins by either negative regulation by E3 ligases or positive regulation of DUBs, respectively, promote tumorigenesis, it is necessary to suppress these DUBs by applying appropriate inhibitors or small molecules. Therefore, we propose that the DUBs and their inhibitors related to the Warburg effect are potential anticancer targets.
Highlights
Cellular respiration is the process by which living organisms decompose organic matter to inorganic matter for producing energy required for survival
A recent study found that a lack of glucose in cancer cells does not reduce ATP levels; blocking fatty acid oxidation (FAO) showed no effect in normal cells but reduced ATP production in cancer cells by 40% [38]
Further studies are required to determine which pathways among glucose, glutamine, and fatty acid metabolism are primarily used by cancer cells to produce ATP
Summary
Cellular respiration is the process by which living organisms decompose organic matter to inorganic matter for producing energy required for survival. Glucose is converted to pyruvate through glycolysis in the cytoplasm, and the pyruvate enters the mitochondria where it is completely degraded [2]. This process requires oxygen, and 38 ATPs are produced from one molecule of glucose: 2 ATPs during glycolysis, 2 ATPs in the TCA cycle, and 34 ATPs in the electron transport system [3]. The cancer cells require more glucose molecules than normal cells to obtain enough energy to survive. Ubiquitin molecules attached to the substrate form a polyubiquitin chain, regulate the activity and function of the substrate protein, and induce degradation through the 26S proteasome [9]. HIF-1α is upregulated, but HIF-2α is downregulated [22]
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