The ubiquitin ligase TRIM56 inhibits ovarian cancer progression by targeting vimentin
| Autor: | Lei Zhao, Ping Zhang, Xiao-jie Su, Bing Zhang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Epithelial-Mesenchymal Transition Time Factors endocrine system diseases Physiology Ubiquitin-Protein Ligases Clinical Biochemistry Vimentin Transfection Gene Expression Regulation Enzymologic Metastasis Tripartite Motif Proteins 03 medical and health sciences 0302 clinical medicine Ubiquitin Cell Movement Cell Line Tumor Ovarian carcinoma medicine Humans Neoplasm Invasiveness Epithelial–mesenchymal transition Neoplasm Metastasis Ovarian Neoplasms biology Cell Biology medicine.disease Ubiquitin ligase Gene Expression Regulation Neoplastic 030104 developmental biology Proteasome 030220 oncology & carcinogenesis Proteolysis biology.protein Cancer research Female RNA Interference Ovarian cancer Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 233:2420-2425 |
| ISSN: | 0021-9541 |
| DOI: | 10.1002/jcp.26114 |
| Popis: | Tumor metastasis is responsible for 90% of all cancer-related deaths. Epithelial to mesenchymal transition (EMT) is an important prerequisite for tumor metastasis. One of the important mediators of EMT and cancer progression in ovarian cancer is the vimentin protein. The objective of the current study was to evaluate the molecular mechanism that regulates vimentin expression in ovarian cancer cells. Vimentin was robustly induced in the ovarian cancer cell line SKOV-3 compared to normal ovarian epithelial cell line Moody and the induction was not due to transcriptional upregulation. Treatment with the proteasomal inhibitor MG-132 revealed that vimentin is actively degraded by the proteasome in Moody cells and stabilized in the SKOV-3 cell line. Mass spectrometric analysis of vimentin immunoprecipitate of MG-132 treated Moody cells revealed candidate ubiquitin ligases associated with vimentin. RNAi mediated silencing of the candidate ubiquitin in Moody cells and concurrent overexpression of the candidate ubiquitin ligases in SKOV-3 confirmed that TRIM56 is the ubiquitin ligase that is degrading vimentin in Moody cells. RNAi mediated silencing of TRIM56 in Moody cells and ectopic overexpression of TRIM56 in SKOV-3 cells, respectively, significantly up- and down-regulated in vitro migration and invasion in these cells. Analysis of TRIM56 transcript level and vimentin protein expression in 25 patients with ovarian carcinoma confirmed an inverse correlation between TRIM56 and vimentin expression. Cumulatively, our data reveals for the first time a novel post-translational regulatory mechanism of regulating vimentin expression, EMT, and metastatic progression in ovarian cancer cells. |
| Databáze: | OpenAIRE |
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