RNF185 modulates JWA ubiquitination and promotes gastric cancer metastasis
| Autor: | Junjie Chen, Donglin Yan, Shouyu Wang, Yan Zhou, Zhangding Wang, Danping Qiu, Ruiwen Zhang, Aiping Li, Jianwei Zhou, Qiang Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Ubiquitin-Protein Ligases Mice Nude law.invention Metastasis Mitochondrial Proteins 03 medical and health sciences Mice Ubiquitin In vivo law Cell Movement Stomach Neoplasms Cell Line Tumor medicine Animals Humans Neoplasm Metastasis Molecular Biology Heat-Shock Proteins Mice Inbred BALB C biology Chemistry Intracellular Signaling Peptides and Proteins Ubiquitination Cancer Membrane Transport Proteins Cell migration medicine.disease In vitro Ubiquitin ligase Neoplasm Proteins Gene Expression Regulation Neoplastic 030104 developmental biology biology.protein Cancer research Molecular Medicine Suppressor Female |
| Zdroj: | Biochimica et biophysica acta. Molecular basis of disease. 1864(5 Pt) |
| ISSN: | 0925-4439 |
| Popis: | Gastric cancer (GC) is one of the most common malignant cancers worldwide. Metastasis leads to poor prognoses in GC patients in advanced stages. Our previous studies have demonstrated that JWA functions as a tumour suppressor and that low expression of JWA in GC tissues is significantly correlated with shorter overall survival (OS) as well as with advanced clinicopathologic features in patients. However, the mechanism of dysregulation of JWA in cancers is not clear. In the present study, we found that an E3 ubiquitin ligase, RNF185, directly interacted with JWA and promoted its ubiquitination at the K158 site, resulting in subsequent degradation. Moreover, the protein level of RNF185 was negatively correlated with JWA in tumour tissues from GC patients. High RNF185 expression was significantly correlated with shorter OS. Additionally, increased RNF185 expression facilitated GC cell migration in vitro and promoted GC metastasis in vivo by downregulating JWA expression. However, this effect was reversed by replenishment of JWA. In conclusion, our findings highlight the following: (1) RNF185 promotes GC metastasis by mediating JWA degradation via a ubiquitin-proteasome pathway; (2) the K158 site of JWA is essential for its ubiquitination in GC cells. These findings suggest that RNF185 is a novel candidate prognostic marker and potential therapeutic target for GC. |
| Databáze: | OpenAIRE |
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