| 论文题目: | Chaperone gp96 mediates ER-alpha36 cell membrane expression |
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| 作者: | Hou Junwei, Deng Mengmeng, Li Xin, Liu Weiwei, Chu Xiaoyu, Wang Jing, Chen Feng*, and Meng Songdong*. |
| 联系作者: | |
| 刊物名称: | Oncotarget |
| 期: | 31 |
| 卷: | 6 |
| 页: | 31857-67 |
| 年份: | 2015 |
| 影响因子: | 6.368 |
| 论文下载: | 下载地址 |
| 摘要: | ER (estrogen receptor)-alpha36, a variant of human ERalpha, activates non-genomic cell signaling pathways. ER-alpha36 on the cell membrane plays a role in breast cancer growth and development, and contributes to tamoxifen resistance. However, it is not understood how cell membrane expression of ER-alpha36 is regulated. In this study, we investigated the role of cell membrane glycoprotein 96 (mgp96) in the regulation of ER-alpha36 expression and signaling. We found that the C-terminal domain of mgp96 directly interacts with ER-alpha36 on the cell membrane of breast tumor cells. This interaction stabilizes the ER-alpha36 protein, thereby increasing its signaling, which, in turn, increases tumor cell growth and invasion. Moreover, targeting mgp96 with siRNA or monoclonal antibody (mAb) blocks the mgp96-ER-alpha36 interaction and inhibits breast cancer growth and invasion both in vitro and in vivo. These results provide insights into the modulation of cell membrane ER-alpha36 expression and suggest that mgp96 could be a potential therapeutic target for ER-alpha36-overexpressing breast cancer. |
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