Blockage of conformational changes of heat shock protein gp96 on cell membrane by a alpha-helix peptide inhibits her2 dimerization and signaling in breast cancer
文献类型：期刊论文
| 作者 | Li, Xin1,2; Wang, Baozhong3; Liu, Weiwei1,2; Gui, Mingming1; Peng, Zheng4; Meng, Songdong1 |
| 刊名 | Plos one
 |
| 出版日期 | 2015-04-21 |
| 卷号 | 10期号:4页码:12 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0124647 |
| 通讯作者 | Peng, zheng(zihpeng@sina.com) |
| 英文摘要 | Cell membrane translocation of heat shock protein gp96 from the endoplasmic reticulum has been observed in multiple tumors and is associated with tumor malignancy. however, the cancer-intrinsic function and the related mechanism of cell membrane gp96 as a pro-on-cogenic chaperone remain further elucidated. in this study, we found that inhibition of gp96 intramolecular conformational changes by a single alpha-helix peptide p37 dramatically increased its binding to her2, whereas decreased her2 dimerization, phosphorylation and downstream signaling. targeting cell membrane gp96 promoted her2 ubiquitination and subsequent lysosomal degradation, which led to decreased cell growth and increased apoptosis, and inhibited tumor growth in vivo. we also demonstrate that gp96 inhibitory peptide p37 synergized with trastuzumab to suppress cell growth and induce apoptosis. our work demonstrates that blocking gp96 conformational changes directs her2 for cellular degradation, and represents a new therapeutic strategy for inhibiting her2 signaling in cancer. |
| WOS关键词 | CHAPERONE GP96 ; THERAPEUTIC-TARGET ; GRP94 ; HOMEOSTASIS ; GP96/GRP94 ; DOMAIN |
| WOS研究方向 | Science & Technology - Other Topics |
| WOS类目 | Multidisciplinary Sciences |
| 语种 | 英语 |
| WOS记录号 | WOS:000353212600078 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2376505 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Peng, Zheng |
| 作者单位 | 1.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Anhui Univ, Sch Life Sci, Hefei 230039, Peoples R China 4.Chinese Peoples Liberat Army Gen Hosp, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xin,Wang, Baozhong,Liu, Weiwei,et al. Blockage of conformational changes of heat shock protein gp96 on cell membrane by a alpha-helix peptide inhibits her2 dimerization and signaling in breast cancer[J]. Plos one,2015,10(4):12. |
| APA | Li, Xin,Wang, Baozhong,Liu, Weiwei,Gui, Mingming,Peng, Zheng,&Meng, Songdong.(2015).Blockage of conformational changes of heat shock protein gp96 on cell membrane by a alpha-helix peptide inhibits her2 dimerization and signaling in breast cancer.Plos one,10(4),12. |
| MLA | Li, Xin,et al."Blockage of conformational changes of heat shock protein gp96 on cell membrane by a alpha-helix peptide inhibits her2 dimerization and signaling in breast cancer".Plos one 10.4(2015):12. |
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来源：中国科学院大学
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