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Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect

Journal

Publisher

MDPI
DOI: 10.3390/ijms22126173

Keywords

anaerobic glycolysis; anticancer; hypoxia; small molecules; ubiquitin-proteasome system (UPS)

Funding

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [RF-2020R1I1A207500312]

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Cancer is characterized by abnormal cell growth and proliferation, with the Warburg effect playing a significant role in the metabolic processes of cancer cells. Various signaling factors regulate the glycolysis pathway in cancer cells through the ubiquitin-proteasome system, and DUBs can act as both oncogenes and tumor suppressors depending on the target protein. Targeting DUBs and their inhibitors associated with the Warburg effect may hold promise as potential anticancer strategies.
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.

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