Department of Biomedical Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Korea.
Int J Mol Sci. 2021 Jun 8;22(12):6173. doi: 10.3390/ijms22126173.
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.
癌症是一种细胞生长和增殖的紊乱,其特征是正常细胞内存在不同的代谢途径。沃伯格效应是癌细胞中的一种主要代谢过程,影响细胞的反应,如增殖和凋亡。各种信号因子下调/上调癌细胞中糖酵解途径的因子,这些信号因子通过泛素-蛋白酶体系统(UPS)被泛素化/去泛素化。根据靶蛋白的不同,DUB 既可以作为癌蛋白,也可以作为肿瘤抑制因子。由于肿瘤抑制因子的降解和癌蛋白的稳定分别由 E3 连接酶的负调控或 DUB 的正调控来促进肿瘤发生,因此有必要通过应用适当的抑制剂或小分子来抑制这些 DUB。因此,我们提出与沃伯格效应相关的 DUB 及其抑制剂是潜在的抗癌靶点。