Deubiquitinase USP13 promotes the epithelial-mesenchymal transition and metastasis in gastric cancer by maintaining Snail protein

Zhang, Ting; Zheng, Jianbao; Qiao, Liang; Zhao, Wei

doi:10.1016/j.prp.2021.153705

Cited by 15 publications

(14 citation statements)

References 31 publications

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“…It has been reported that c-Myc can be de-ubiquitinated by USP13 [ 33 ]. In addition, USP13 has been reported to de-ubiquitinate another EMT-TF, Snail [ 62 ]. Therefore, we set out to investigate whether USP13 may affect Twist1.…”

Section: Discussionmentioning

confidence: 99%

USP13 promotes breast cancer metastasis through FBXL14-induced Twist1 ubiquitination

Zhao

Huo

et al. 2023

Cell Oncol.

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Purpose Epithelial-to-mesenchymal transition (EMT) is an important cause of high mortality in breast cancer. Twist1 is one of the EMT transcription factors (EMT-TFs) with a noticeably short half-life, which is regulated by proteasome degradation pathways. Recent studies have found that USP13 stabilizes several specific oncogenic proteins. As yet, however, the relationship between Twist1 and USP13 has not been investigated. Methods Co-Immunoprecipitation, GST-pulldown, Western blot, qRT-PCR and immunofluorescence assays were used to investigate the role of USP13 in de-ubiquitination of Twist1. Chromatin immunoprecipitation and Luciferase reporter assays were used to investigate the role of Twist1 in inhibiting USP13 reporter transcription. Scratch wound healing, cell migration and invasion assays, and a mouse lung metastases assay were used to investigate the roles of USP13 and Twist1 in promoting breast cancer metastasis. Results We found that Twist1 can be de-ubiquitinated by USP13. In addition, we found that the protein levels of Twist1 dose-dependently increased with USP13 overexpression, while USP13 knockdown resulted in a decreased expression of endogenous Twist1. We also found that USP13 can directly interact with Twist1 and specifically cleave the K48-linked polyubiquitin chains of Twist1 induced by FBXL14. We found that the effect of USP13 in promoting the migration and invasion capacities of breast cancer cells can at least partly be achieved through its regulation of Twist1, while Twist1 can inhibit the transcriptional activity of USP13. Conclusions Our data indicate that an interplay between Twist1 and USP13 can form a negative physiological feedback loop. Our findings show that USP13 may play an essential role in breast cancer metastasis by regulating Twist1 and, as such, provide a potential target for the clinical treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

USP13 promotes breast cancer metastasis through FBXL14-induced Twist1 ubiquitination

Zhao

Huo

et al. 2023

Cell Oncol.

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“…In gastric cancer, the high expression of USP13 is associated with high invasion, contributing to reduced survival rate of patients. It is supposed that USP13 deubiquitinated and stabilized Snail protein, promoting metastasis in gastric cancer cells ( Zhang et al, 2022 ). Collectively, due to its role in a variety of tumors and neurodegenerative diseases, USP13 has emerged as a potential therapeutic target for diverse tumors.…”

Section: Cellular Function Of Usp13mentioning

confidence: 99%

USP13: Multiple Functions and Target Inhibition

Yang

Zhang

et al. 2022

Front. Cell Dev. Biol.

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As a deubiquitination (DUB) enzyme, ubiquitin-specific protease 13 (USP13) is involved in a myriad of cellular processes, such as mitochondrial energy metabolism, autophagy, DNA damage response, and endoplasmic reticulum-associated degradation (ERAD), by regulating the deubiquitination of diverse key substrate proteins. Thus, dysregulation of USP13 can give rise to the occurrence and development of plenty of diseases, in particular malignant tumors. Given its implications in the stabilization of disease-related proteins and oncology targets, considerable efforts have been committed to the discovery of inhibitors targeting USP13. Here, we summarize an overview of the recent advances of the structure, function of USP13, and its relations to diseases, as well as discovery and development of inhibitors, aiming to provide the theoretical basis for investigation of the molecular mechanism of USP13 action and further development of more potent druggable inhibitors.

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“…Toll-like receptor 4 (TLR4), an essential sensor involved in carcinogenesis, is also a substrate of USP13, and TLR4/myeloid differentiation factor 88 (MyD88)/NF-κB pathway activation facilitates the proliferation, migration and invasion of HCC cells ( Chen et al, 2008 ; Gao et al, 2020 ). Additionally, USP13 was upregulated in gastric cancer, and this upregulation may promote advanced tumor stage by stabilizing Snail, an inducer of epithelial–mesenchymal transition (EMT) and metastasis ( Zhang et al, 2022b ). In addition to the abovementioned oncogenic proteins, USP13 also accelerates tumor progression by regulating cancer metabolism.…”

Section: Ubiquitin Specific Protease-13 In Cancersmentioning

confidence: 99%

Role of USP13 in physiology and diseases

Wang

Sun

Xia

et al. 2022

Front. Mol. Biosci.

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Ubiquitin specific protease (USP)-13 is a deubiquitinase that removes ubiquitin from substrates to prevent protein degradation by the proteasome. Currently, the roles of USP13 in physiology and pathology have been reported. In physiology, USP13 is highly associated with cell cycle regulation, DNA damage repair, myoblast differentiation, quality control of the endoplasmic reticulum, and autophagy. In pathology, it has been reported that USP13 is important in the pathogenesis of infection, inflammation, idiopathic pulmonary fibrosis (IPF), neurodegenerative diseases, and cancers. This mini-review summarizes the most recent advances in USP13 studies involving its pathophysiological roles in different conditions and provides new insights into the prevention and treatment of relevant diseases, as well as further research on USP13.

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Deubiquitinase USP13 promotes the epithelial-mesenchymal transition and metastasis in gastric cancer by maintaining Snail protein

Cited by 15 publications

References 31 publications

USP13 promotes breast cancer metastasis through FBXL14-induced Twist1 ubiquitination

USP13 promotes breast cancer metastasis through FBXL14-induced Twist1 ubiquitination

USP13: Multiple Functions and Target Inhibition

Role of USP13 in physiology and diseases

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