COP9 signalosome subunit 5 regulates cancer metastasis by deubiquitinating SNAIL
| Autor: | Yusuke Iwakami, Naoki Kaneto, Yoshihiro Hayakawa, Junya Fukuoka, Kensuke Watanabe, Shinichiro Kato, Takashi Hori, Hiroaki Sakurai, Satoru Yokoyama, Ikuo Saiki |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Snail Biology Metastasis Deubiquitinating enzyme 03 medical and health sciences Downregulation and upregulation Ubiquitin biology.animal parasitic diseases medicine metastasis COP9 signalosome deubiquitination Transcription factor SNAIL fungi Cancer medicine.disease lung cancer 030104 developmental biology Oncology Cancer research biology.protein COPS5 Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Cancer metastasis is a major cause of mortality in cancer patients. The transcription factor SNAIL plays an important role in cancer metastasis and progression, and its expression is tightly regulated by the ubiquitin-proteasome system through the balance between ubiquitin ligases and deubiquitinating enzymes. While several ubiquitin ligases of SNAIL have been identified, it is not yet clear regarding deubiquitinating enzyme. In this study, we identified COP9 signalosome subunit 5 (COPS5) as a deubiquitinating enzyme of SNAIL by using siRNA library screening. COPS5 downregulation significantly reduced the expression of SNAIL and impaired the metastatic potential of lung cancer cells both in vitro and in vivo. Importantly, we demonstrated that COPS5 binds to SNAIL and stabilizes its expression by deubiquitination. Furthermore, we observed the positive correlation between COPS5 and SNAIL expression in the clinical tissue samples of lung adenocarcinomas by using tissue microarray analysis. These findings provide strong evidence that COPS5 can be a new therapeutic target for cancer metastasis as a deubiquitinating enzyme of SNAIL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|