| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○著者 (必須): | 1. | 吉丸 哲郎 ([徳島大学.先端酵素学研究所.重点研究部門])
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| 2. | (英) Aihara Keisuke (日) 粟飯原 圭佑 (読) あいはら けいすけ
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| ○学籍番号 (推奨): | □ | ****
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| 3. | 小松 正人
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| 4. | 松下 洋輔
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| 5. | (英) Okazaki Yasumasa (日) (読)
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| 6. | (英) Toyokuni Shinya (日) (読)
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| 7. | (英) Honda Junko (日) (読)
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| 8. | (英) Sasa Mitsunori (日) (読)
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| 9. | (英) Miyoshi Yasuo (日) 三好 康雄 (読)
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| 10. | 大髙 章
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| 11. | 片桐 豊雅
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| ○題名 (必須): | □ | (英) Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast cancer therapeutics. (日)
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| ○要約 (任意): | □ | (英) Estradiol (E2) and the oestrogen receptor-alpha (ER) 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/ER signalling modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2 interaction using the ER activity-regulator synthetic peptide (ERAP: 165-177 amino acids), derived from -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 -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. (日)
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| ○誌名 (必須): | □ | Scientific Reports ([Nature Publishing Group])
(eISSN: 2045-2322)
| ○ISSN (任意): | □ | 2045-2322
ISSN: 2045-2322
(eISSN: 2045-2322) Title: Scientific reportsTitle(ISO): Sci RepPublisher: Nature Portfolio (NLM Catalog)
(Scopus)
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| ○巻 (必須): | □ | 7
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| ○号 (必須): | □ | 1
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| ○頁 (必須): | □ | 1821 1821
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| ○年月日 (必須): | □ | 西暦 2017年 5月 12日 (平成 29年 5月 12日)
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| ○DOI (任意): | □ | 10.1038/s41598-017-01951-6 (→Scopusで検索)
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| ○PMID (任意): | □ | 28500289 (→Scopusで検索)
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| ○機関リポジトリ : | □ | 112387
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| ○備考 (任意): | 1. | (英) PublicationType: Journal Article (日)
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