The Ubiquitin-Proteasome System in Tumor Metabolism

Metabolic reprogramming, which is considered a hallmark of cancer, can maintain the homeostasis of the tumor environment and promote the proliferation, survival, and metastasis of cancer cells. For instance, increased glucose uptake and high glucose consumption, known as the "Warburg effect," play an essential part in tumor metabolic reprogramming. In addition, fatty acids are harnessed to satisfy the increased requirement for the phospholipid components of biological membranes and energy. Moreover, the anabolism/catabolism of amino acids, such as glutamine, cystine, and serine, provides nitrogen donors for biosynthesis processes, development of the tumor inflammatory environment, and signal transduction. The ubiquitin-proteasome system (UPS) has been widely reported to be involved in various cellular biological activities. A potential role of UPS in the metabolic regulation of tumor cells has also been reported, but the specific regulatory mechanism has not been elucidated. Here, we review the role of ubiquitination and deubiquitination modification on major metabolic enzymes and important signaling pathways in tumor metabolism to inspire new strategies for the clinical treatment of cancer.