No abstract

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.

The catenin beta 1 gene (CTNNB1) plays a crucial role in the malignant progression of various cancers. Emerging studies have suggested that its hyperactivation is closely related to the occurrence and development of bladder cancer(BCa). Here, we report that UCHL3(Ubiquitin C-terminal hydrolase L3), a deubiquitinating enzyme promotes the development of bladder cancer through Wnt signaling pathway by interacting with and stabilizing CTNNB1 in vitro and in vivo. GSEA analysis showed that UCHL3 was highly associated with Wnt signaling pathway, and it was validated by luciferase reporter assays and RT-PCR, which found that its functions depend on its deubiquitinating activity. We also found that the overexpression of UCHL3 boosted the bladder cancer cells proliferation, invasion and migration, while the depletion of UCHL3 in bladder cancer cells delayed the tumor tumorigenesis in vitro and in vivo. Especially, Uchl3-deficient mice were less susceptible to bladder tumorigenesis. Additionally, UCHL3 was highly expressed in bladder cancer and associated with advanced clinicopathological parameters. These findings provided direct insight into the molecular mechanism of the functions of UCHL3 in bladder cancer, and provided new target for therapeutic approach against bladder cancer.