title: Targeting Deubiquitinating Enzymes in Glioblastoma Multiforme: Expectations and Challenges.
abstract: Glioblastoma (GBM) is regarded as the most common primary intracranial neoplasm. Despite standard treatment with tumor resection and radiochemotherapy, the outcome remains gloomy. It is evident that a combination of oncogenic gain of function and tumor-suppressive loss of function has been attributed to glioma initiation and progression. The ubiquitin-proteasome system is a well-orchestrated system that controls the fate of most proteins by striking a dynamic balance between ubiquitination and deubiquitination of substrates, having a profound influence on the modulation of oncoproteins, tumor suppressors, and cellular signaling pathways. In recent years, deubiquitinating enzymes (DUBs) have emerged as potential anti-cancer targets due to their targeting several key proteins involved in the regulation of tumorigenesis, apoptosis, senescence, and autophagy. This review attempts to summarize recent studies of GBM-associated DUBs, their roles in various cellular processes, and discuss the relation between DUBs deregulation and gliomagenesis, especially how DUBs regulate glioma stem cells pluripotency, microenvironment, and resistance of radiation and chemotherapy through core stem-cell transcriptional factors. We also review recent achievements and progress in the development of potent and selective reversible inhibitors of DUBs, and attempted to find a potential GBM treatment by DUBs intervention.
authors: Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.|National Centers for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
authors: Wei-Lin
authors: WL
authors: Jin
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, P. R. China.
authors: Xiao-Yuan
authors: XY
authors: Mao
authors: Department of Neurosurgery, General Hospital of Jinan Military Command, Jinan, 250031, P. R. China.
authors: Guan-Zhong
authors: GZ
authors: Qiu
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D000072017:Deubiquitinating Enzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005909:Glioblastoma / Q000201:enzymology* / Q000628:therapy*; D006801:Humans; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D000072017:Deubiquitinating Enzymes
keywords: DUB inhibitor; DUBs; glioblastoma; glioma stem cells; proteasome