| Item type |
文献 / Documents(1) |
| 公開日 |
2018-11-12 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
関連識別子 |
https://doi.org/10.1038/s41598-017-01951-6 |
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|
関連名称 |
10.1038/s41598-017-01951-6 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast cancer therapeutics |
| 著者 |
吉丸, 哲郎
アイハラ, ケイスケ
小松, 正人
松下, 洋輔
オカザキ, ヤスマサ
トヨクニ, シンヤ
ホンダ, ジュンコ
ササ, ミツノリ
ミヨシ, ヤスオ
大髙, 章
片桐, 豊雅
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| 抄録 |
|
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内容記述 |
Estradiol (E2) and the oestrogen receptor-alpha (ERα) signalling pathway play pivotal roles in the proliferative activity of breast cancer cells. Recent findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ERα signalling modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2 interaction using the ERα activity-regulator synthetic peptide (ERAP: 165–177 amino acids), derived from α-helical BIG3 sequence, resulted in a significant anti-tumour effect. However, the duration of this effect was very short for viable clinical application. We developed the chemically modified ERAP using stapling methods (stapledERAP) to improve the duration of its antitumour effects. The stapledERAP specifically inhibited the BIG3-PHB2 interaction and exhibited long-lasting suppressive activity. Its intracellular localization without the membrane-permeable polyarginine sequence was possible via the formation of a stable α-helix structure by stapling. Tumour bearing-mice treated daily or weekly with stapledERAP effectively prevented the BIG3-PHB2 interaction, leading to complete regression of E2-dependent tumours in vivo. Most importantly, combination of stapledERAP with tamoxifen, fulvestrant, and everolimus caused synergistic inhibitory effects on growth of breast cancer cells. Our findings suggested that the stapled ERAP may be a promising anti-tumour drug to suppress luminal-type breast cancer growth. |
| 書誌情報 |
en : Scientific Reports
巻 7,
p. 1821,
発行日 2017-05-12
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| 収録物ID |
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|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20452322 |
| 出版者 |
|
|
出版者 |
Springer Nature |
| 備考 |
|
|
値 |
Supplementary Information : srep_7_1821_s1.pdf |
| 権利情報 |
|
|
権利情報 |
© The Author(s) 2017 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| EID |
|
|
識別子 |
333838 |
| 言語 |
|
|
言語 |
eng |
srep_7_1821.pdf (4.14 MB)
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