The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy

Wang, Xuemei; Zhang, Ying; Wu, Yao; Cheng, Hongjing; Wang, Xueju

doi:10.3389/fimmu.2023.1202633

Cited by 3 publications

(3 citation statements)

References 174 publications

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“…Because ubiquitination or deubiquitination of certain molecules can be cellular context-dependent, E3 ligases and DUBs targeting PD-1/PD-L1 in other tumors should be further verified in bladder cancer. Several E3 ligases and DUBs, especially DUBs, can be directly targeted by small molecular drugs; thus the combination of specific inhibitors and ICIs might be attractive and promising for enhancing ICI treatment effects ( 176 ). Notably, deubiquitinating enzymes are potential biomarkers for treatment selection and prognosis prediction ( 177 ).…”

Section: Role Of E3 Ligases and Dubs In Immunotherapy Of Bladder Cancermentioning

confidence: 99%

E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies

Wang

Zhang

et al. 2023

Front. Immunol.

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With the rapidly increasing incidence of bladder cancer in China and worldwide, great efforts have been made to understand the detailed mechanism of bladder cancer tumorigenesis. Recently, the introduction of immune checkpoint inhibitor-based immunotherapy has changed the treatment strategy for bladder cancer, especially for advanced bladder cancer, and has improved the survival of patients. The ubiquitin–proteasome system, which affects many biological processes, plays an important role in bladder cancer. Several E3 ubiquitin ligases and deubiquitinases target immune checkpoints, either directly or indirectly. In this review, we summarize the recent progress in E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and further highlight the implications for bladder cancer immunotherapies.

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Section: Role Of E3 Ligases and Dubs In Immunotherapy Of Bladder Cancermentioning

confidence: 99%

E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies

Wang

Zhang

et al. 2023

Front. Immunol.

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“…Post-translational modifications, particularly acetylation, have been documented in BLCA 18 . Notably, attention has been given to ACAT1, an enzyme localized in the mitochondrion that was initially recognized for its pivotal role in the rare genetic disease β-ketothiolase deficiency.…”

Section: Introductionmentioning

confidence: 99%

ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway

Wang,

Shan

et al. 2024

J. Cancer

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Acetyl-CoA acetyltransferase 1 (ACAT1) plays a significant role in the regulation of gene expression and tumorigenesis. However, the biological role of ACAT1 in bladder cancer (BLCA) has yet to be elucidated. This research aimed to elucidate the bioinformatics features and biological functions of ACAT1 in BLCA. Here, we demonstrate that ACAT1 is elevated in BLCA tissues and is correlated with specific clinicopathological features and an unfavorable prognosis for survival in BLCA patients. ACAT1 was identified as an independent risk factor in BLCA. Phenotypically, both in vitro and in vivo , ACAT1 knockdown suppressed BLCA cell proliferation and migration, while ACAT1 overexpression had the opposite effect. Mechanistic assays revealed that ACAT1 enhances BLCA cell proliferation and metastasis through the AKT/GSK3β/c-Myc signaling pathway by modulating the cell cycle and EMT. Taken together, the results of our study reveal that ACAT1 is an oncogenic driver in BLCA that enhances tumor proliferation and metastasis, indicating its potential as a diagnostic and therapeutic target for this disease.

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“…In humans, genetic alterations, abnormal expression or dysfunction of E3 ubiquitin ligases and DUBs determine the onset and progression of many pathological conditions such as neurodegenerative diseases, immune-related pathologies and cancer [ 8 , 48 , 49 , 50 ]. For these reasons, the study of the ubiquitination machinery, as well as the molecular mechanisms underlying its activity and regulation, has been an area of intense research over the last two decades with the aim of developing new therapeutic approaches to treat such pathological conditions [ 50 , 51 , 52 , 53 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy

Spano,

Catara

2023

Cells

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Ubiquitination is a reversible post-translational modification based on the chemical addition of ubiquitin to proteins with regulatory effects on various signaling pathways. Ubiquitination can alter the molecular functions of tagged substrates with respect to protein turnover, biological activity, subcellular localization or protein–protein interaction. As a result, a wide variety of cellular processes are under ubiquitination-mediated control, contributing to the maintenance of cellular homeostasis. It follows that the dysregulation of ubiquitination reactions plays a relevant role in the pathogenic states of human diseases such as neurodegenerative diseases, immune-related pathologies and cancer. In recent decades, the enzymes of the ubiquitin–proteasome system (UPS), including E3 ubiquitin ligases and deubiquitinases (DUBs), have attracted attention as novel druggable targets for the development of new anticancer therapeutic approaches. This perspective article summarizes the peculiarities shared by the enzymes involved in the ubiquitination reaction which, when deregulated, can lead to tumorigenesis. Accordingly, an overview of the main pharmacological interventions based on targeting the UPS that are in clinical use or still in clinical trials is provided, also highlighting the limitations of the therapeutic efficacy of these approaches. Therefore, various attempts to circumvent drug resistance and side effects as well as UPS-related emerging technologies in anticancer therapeutics are discussed.

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The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy

Cited by 3 publications

References 174 publications

E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies

E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies

ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway

Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy

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