USP10 regulates the stability of the EMT-transcription factor Slug/SNAI2

Ouchida, Amanda Tomie; Kacal, Merve; Zheng, Adi; Ambroise, Gorbatchev; Zhang, Boxi; Norberg, Erik; Vakifahmetoglu-Norberg, Helin

doi:10.1016/j.bbrc.2018.05.156

Cited by 34 publications

(25 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that expression of these factors is tightly controlled by DUBs. Snail protein can be deubiquitinated and stabilized by USP26, USP11, USP10, USP37 or OTUB1 [55][56][57][58][59]. Slug can be stabilized by USP10 and DUB3 [55,60].…”

Section: Discussionmentioning

confidence: 99%

The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness

et al. 2020

Cancers

View full text Add to dashboard Cite

Lung cancer stem cells (CSCs) play a pivotal role in tumor development, drug resistance, metastasis and recurrence of lung cancer. Thus, it is of great importance to study the mechanism by which CSCs are regulated. In this study, we demonstrate that the deubiquitinase USP4 is critically important in promoting lung cancer stemness. Silencing of USP4 leads to reduction of Oct4 and Sox2 expression, decreased CD133+ cell population and inhibition of tumorsphere formation. Conversely, ectopic expression of USP4 significantly enhances lung cancer cell stemness, which is effectively rescued by simultaneous silencing of Twist1. Mechanistically, we identified USP4 as a novel deubiquitinase of Twist1. USP4 binds to, deubiquitinates and stabilizes Twist1 protein. Furthermore, we show that USP4 expression is elevated in human lung cancer specimens and is positively correlated with Twist1 expression. High expression of USP4/Twist1 is associated with poor clinical outcomes of lung cancer patients. Together, this study highlights an important role for USP4 in lung cancer stemness and suggests USP4 as a potential target for lung cancer diagnosis and treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…In hepatocellular cancer, USP10, as a tumour suppressor, negatively regulates mTORC1 activation and AKT phosphorylation by stabilising AMPKα and PTEN in HCC cells ( 13 ). USP10 is also a regulator of the EMT-transcription factor SLUG and of cell migration ( 25 ). In the NFALD model, USP10 regulates hepatic steatosis by interacting with SIRT6 and inhibiting its ubiquitination and degradation.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-Specific Peptidase 10 Protects Against Hepatic Ischaemic/Reperfusion Injury via TAK1 Signalling

et al. 2020

View full text Add to dashboard Cite

Ubiquitin-specific peptidase 10 (USP10) protein is a deubiquitination enzyme involved in many important biological processes. However, the function of USP10 in hepatic ischaemic/reperfusion (I/R) injury remains unknown. The aim of this study was to explore the role of USP10 in hepatic I/R injury. USP10 Heterozygote mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP10 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP10 was significantly downregulated in the livers of mice after hepatic I/R injury and in hepatocytes subjected to hypoxia/reoxygenation stimulation. USP10 Heterozygote mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the NF-κB signalling pathway and increased hepatocyte apoptosis. Additionally, USP10 overexpression inhibited hepatocyte inflammation and apoptosis in hepatic I/R injury in vitro and in vivo . Mechanistically, our study demonstrated that USP10 knockdown exerted its detrimental effects on hepatic I/R injury by inducing activation of the transforming growth factor β-activated kinase 1 (TAK1)-JNK/p38 signalling pathways. TAK1 was required for USP10 function in hepatic I/R injury as TAK1 inhibition abolished USP10 function in vitro . In conclusion, our study demonstrated that USP10 plays a protective role in hepatic I/R injury by inhibiting the activation of the TAK1-JNK/p38 signalling pathways. Modulation of USP10/TAK1 might be a promising strategy to prevent this pathological process.

show abstract

“…Nevertheless, the roles of USP10 in cancer metastasis remain to be clarified. Ouchida et al (2018) identified that USP10 functions as a deubiquitinase and regulator of the EMT-transcription factor Slug to promote cell migration in multiple tumor cells, including non-small-cell lung carcinoma, ovarian cancer, fibrosarcoma, and breast cancer. However, the functions of USP10 on HCC metastasis are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Deubiquitinating enzyme USP10 promotes hepatocellular carcinoma metastasis through deubiquitinating and stabilizing Smad4 protein

et al. 2019

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) has emerged as one of the most prevalent life-threatening cancers, and the high mortality rate is largely due to the metastasis. The sustained activation of Smad4 and transforming growth factor-b (TGF-b) is closely associated with advanced HCC metastasis. However, the regulatory mechanism underlying the aberrant activation of Smad4 and TGF-b pathway remains elusive. In this study, using a functional screen of USPs siRNA library, we identified ubiquitin-specific proteases USP10 as a deubiquitinating enzyme (DUB) that sustains the protein level of Smad4 and activates TGF-b signaling. Further analysis showed that USP10 directly interacts with Smad4 and stabilizes it through the cleavage of its proteolytic ubiquitination, thus promoting HCC metastasis. The suppression of USP10 by either shRNAs or catalytic inhibitor Spautin-1 significantly inhibited the migration of HCC cells, whereas the reconstitution of Smad4 was able to efficiently rescue this defect. Overall, our study not only uncovers the regulatory effect of USP10 on the protein abundance of Smad4, but also indicates that USP10 could be regarded as a potential intervention target for the metastatic HCC in Smad4-positive patients.

show abstract

USP10 regulates the stability of the EMT-transcription factor Slug/SNAI2

Cited by 34 publications

References 17 publications

The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness

The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness

Ubiquitin-Specific Peptidase 10 Protects Against Hepatic Ischaemic/Reperfusion Injury via TAK1 Signalling

Deubiquitinating enzyme USP10 promotes hepatocellular carcinoma metastasis through deubiquitinating and stabilizing Smad4 protein

Contact Info

Product

Resources

About