ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc
文献类型：期刊论文
| 作者 | Zhang, C. ; Zhang, S. ; Zhang, Z. ; He, J. ; Xu, Y. ; Liu, S. |
| 刊名 | ONCOGENE
 |
| 出版日期 | 2014 |
| 卷号 | 33期号:49页码:5582-5591 |
| 关键词 | ROCK c-Myc prostate cancer cells proliferation protein stability |
| ISSN号 | 0950-9232 |
| 中文摘要 | Rho-associated kinase (ROCK) has an essential role in governing cell morphology and motility, and increased ROCK activity contributes to cancer cell invasion and metastasis. Burgeoning data suggest that ROCK is also involved in the growth regulation of tumor cells. However, thus far, the molecular mechanisms responsible for ROCK-governed tumor cell growth have not been clearly elucidated. Here we showed that inhibition of ROCK kinase activity, either by a selective ROCK inhibitor Y27632 or by specific ROCK small interfering RNA (siRNA) molecules, attenuated not only motility but also the proliferation of PC3 prostate cancer cells in vitro and in vivo. Importantly, mechanistic investigation revealed that ROCK endowed cancer cells with tumorigenic capability, mainly by targeting c-Myc. ROCK could increase the transcriptional activity of c-Myc by promoting c-Myc protein stability, and ROCK inhibition reduced c-Myc-mediated expression of mRNA targets (such as HSPC111) and microRNA targets (such as miR-17-92 cluster). We provided evidence demonstrating that ROCK1 directly interacted with and phosphorylated c-Myc, resulting in stabilization of the protein and activation of its transcriptional activity. Suppression of ROCK-c-Myc downstream molecules, such as c-Myc-regulated miR-17, also impaired tumor cell growth in vitro and in vivo. In addition, c-Myc was shown to exert a positive feedback regulation on ROCK by increasing RhoA mRNA expression. Therefore, inhibition of ROCK and its stimulated signaling might prove to be a promising strategy for restraining tumor progression in prostate cancer. |
| WOS记录号 | WOS:000346088700002 |
| 公开日期 | 2015-03-24 |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/9448]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Zhang, C.,Zhang, S.,Zhang, Z.,et al. ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc[J]. ONCOGENE,2014,33(49):5582-5591. |
| APA | Zhang, C.,Zhang, S.,Zhang, Z.,He, J.,Xu, Y.,&Liu, S..(2014).ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc.ONCOGENE,33(49),5582-5591. |
| MLA | Zhang, C.,et al."ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc".ONCOGENE 33.49(2014):5582-5591. |
入库方式： OAI收割
来源：生态环境研究中心
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。