Deubiquitinase USP13 promotes the epithelial-mesenchymal transition and metastasis in gastric cancer by maintaining Snail protein
| Autor: | Wei Zhao, Lina Qiao, Jianbao Zheng, Ting Zhang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Epithelial-Mesenchymal Transition biology Cancer Cell Biology Snail Middle Aged medicine.disease Pathology and Forensic Medicine Deubiquitinating enzyme Metastasis Stomach Neoplasms biology.animal biology.protein medicine Cancer research Humans Female Epithelial–mesenchymal transition Snail Family Transcription Factors Ubiquitin-Specific Proteases Neoplasm Metastasis |
| Zdroj: | Pathology, research and practice. 229 |
| ISSN: | 1618-0631 |
| Popis: | The dynamic balance between ubiquitination and deubiquitination is a key mechanism that regulates protein degradation and maintains cell protein homeostasis. Ubiquitin-specific peptidase 13 (USP13), a deubiquitinase (DUB), regulates various physiological and pathological processes, including cancer. A previous study reported that high USP13 mRNA expression confers poor prognosis in gastric cancer (GC). However, the biological function of USP13 in GC remains unknown. Here, we revealed that USP13 expression was upregulated in GC tissue samples compared to noncancerous tissues. USP13-positive expression was associated with poor differentiation, high invasiveness, and advanced tumor stage. Notably, upregulated USP13 expression was closely correlated with the reduced survival of GC patients. We also confirmed increased USP13 expression in GC cell lines. USP13 knockdown prominently suppressed MGC-803 cell migration and invasion. Conversely, USP13 overexpression markedly enhanced SGC-7901 cell motility. Furthermore, USP13 positively regulates the epithelial-mesenchymal transition (EMT) of GC cells. Interestingly, USP13 remarkably enhanced Snail protein expression but did not affect its mRNA levels in GC cells. We confirmed a positive correlation between USP13 and Snail expression in GC tissues. Mechanistically, USP13 knockdown promoted Snail degradation, which could be blocked by the proteasome inhibitor MG132. USP13 interacted with Snail to deubiquitinate and stabilize Snail in GC cells. Finally, Snail knockdown significantly blocked USP13-induced SGC-7901 cell migration and invasion. In conclusion, USP13 overexpression was frequently detected in GC and contributed to the EMT and metastasis of GC by stabilizing Snail. |
| Databáze: | OpenAIRE |
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