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Updated: Dec 15, 2025
Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples
Published on: May 10, 2015
The multiple roles of deubiquitinases in liver cancer
Xin-You Lv1, Ting Duan2,3,4, Jin Li1
1Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Abstract:
Primary liver cancer ranks the second leading cause of death associated with cancer in the world and therefore a major public health challenge. The mortality rates of liver cancer has been increasing during the past decades with the reality that the alternative therapeutic drugs are not available. Although growing numbers of proteins involved in liver cancer progression have been identified, many of these are not suitable drug targets, which hinders the development of new drugs to cure liver cancer. It is in urgent demand that novel therapeutic approaches should be explored. Deubiquitinases (DUBs), specifically removing ubiquitin chains from the target protein, have showed vital roles for protein homeostasis and quality control by rigidly regulating the balance between ubiquitination and deubiquitination in normal physiology. Recent studies have revealed deregulation or dysfunction of DUBs always associates with cancer and other diseases. Targeting certain DUBs, leading to degradation or loss function of the key oncoproteins, including undruggable ones, seems to provide a potential therapy for cancer patients. In liver cancer, numberous of DUBs are demonstrated to participate in hepatocarcinogenesis, metastasis and so on. Depending on the substrates, some DUBs may suppress liver cancers while others promote. In this review, we primarily summarize the roles of DUBs in liver tumors, and illustrate opportunities for the application of targeting DUBs for cancer therapy.
Insights
Targeting deubiquitinases (DUBs) offers a promising new strategy for liver cancer therapy. Inhibiting specific DUBs can degrade key oncoproteins, addressing the urgent need for novel treatments for this deadly disease.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Primary liver cancer is a leading cause of cancer-related death globally, with increasing mortality rates and limited therapeutic options.
- While many proteins involved in liver cancer are known, few are suitable drug targets, highlighting the need for novel therapeutic strategies.
- Deubiquitinases (DUBs) are crucial for protein homeostasis, regulating ubiquitination/deubiquitination balance, and their dysregulation is linked to cancer.
Purpose of the Study:
- To review the multifaceted roles of deubiquitinases (DUBs) in the development and progression of liver tumors.
- To explore the therapeutic potential of targeting DUBs as a novel strategy for liver cancer treatment.
Main Methods:
- Literature review summarizing current research on DUBs in liver cancer.
- Analysis of DUBs' substrates and their impact on hepatocarcinogenesis and metastasis.
- Evaluation of DUBs as potential drug targets for liver cancer therapy.
Main Results:
- DUBs play diverse roles in liver cancer, with some promoting and others suppressing tumor progression depending on their substrates.
- Dysfunctional DUBs are associated with various cancers, including liver cancer.
- Targeting specific DUBs can lead to the degradation of oncoproteins, including those previously considered undruggable.
Conclusions:
- Deubiquitinases represent a promising class of therapeutic targets for liver cancer.
- Targeting DUBs offers a potential avenue for developing novel treatments for liver cancer, addressing unmet clinical needs.
- Further research into specific DUBs and their roles in liver tumorigenesis is warranted to optimize therapeutic strategies.
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