| RRC ID |
45391
|
| 著者 |
Takamiya R, Takahashi M, Uehara Y, Ariki S, Hashimoto J, Hasegawa Y, Kuroki Y.
|
| タイトル |
The single N-glycan deletion mutant of soluble ErbB3 protein attenuates heregulin β1-induced tumor progression by blocking of the HIF-1 and Nrf2 pathway.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
It has been well documented that activation of the ErbB3-PI3K-Akt pathway is implicated in tumor survival and progression. We previously demonstrated that the single N-glycan deletion mutant of soluble ErbB3 protein (sErbB3 N418Q) attenuates heregulin β1-induced ErbB3 signaling. The active PI3K-Akt pathway augments the nuclear accumulation of hypoxia inducible factor (HIF)-1α, which activates the transcription of many target genes and drives cancer progression. In this study, we focused on the effects of sErbB3 N418Q mutant on nuclear accumulation of HIF-1α. Pretreatment with the sErbB3 N418Q mutant suppressed heregulin β1-induced HIF-1α activation in MCF7 cells. Similar results were also obtained in other breast cancer cell lines, T47D and BT474. Interestingly, these suppressive effects were not observed with the sErbB3 wild type. In addition, pretreatment with the sErbB3 N418Q mutant suppressed the cell migration of MCF7 cells induced by heregulin β1. Furthermore, incubation with heregulin β1 also induced the nuclear accumulation of Nrf2, and this effect was also reduced by the sErbB3 N418Q mutant, but not the sErbB3 wild type. These findings indicated that the sErbB3 N418Q mutant suppressed malignant formation of cancer cells by blocking of the HIF-1α and Nrf2 pathways.
|
| 巻・号 |
454(3)
|
| ページ |
364-8
|
| 公開日 |
2014-11-21
|
| DOI |
10.1016/j.bbrc.2014.10.086
|
| PII |
S0006-291X(14)01895-6
|
| PMID |
25451255
|
| MeSH |
Breast / metabolism
Breast / pathology
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Movement
Disease Progression
Female
Gene Deletion
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
MCF-7 Cells
NF-E2-Related Factor 2 / metabolism*
Neuregulin-1 / metabolism*
Point Mutation*
Receptor, ErbB-3 / chemistry
Receptor, ErbB-3 / genetics*
Receptor, ErbB-3 / metabolism
Signal Transduction*
Solubility
|
| IF |
2.985
|
| 引用数 |
4
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MCF7(RCB1904) |
