The multiple roles of deubiquitinases in liver cancer.

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.