| ○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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| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Ueda T (日) (読)
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| 2. | (英) Nakata Y (日) (読)
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| 3. | (英) Yamasaki N (日) (読)
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| 4. | (英) Oda H (日) (読)
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| 5. | (英) Sentani K (日) (読)
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| 6. | (英) Kanai A (日) (読)
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| 7. | (英) Onishi N (日) (読)
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| 8. | (英) Ikeda K (日) (読)
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| 9. | (英) Sera Y (日) (読)
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| 10. | (英) Honda Z (日) (読)
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| 11. | (英) Tanaka K (日) (読)
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| 12. | 佐田 政隆 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学])
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| 13. | (英) Ogawa S (日) (読)
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| 14. | (英) Yasui W (日) (読)
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| 15. | (英) Saya H (日) (読)
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| 16. | (英) Takita J (日) (読)
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| 17. | (英) Honda H (日) (読)
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| ○題名 (必須): | □ | (英) ALKR1275Q perturbs extracellular matrix, enhances cell invasion and leads to the development of neuroblastoma in cooperation with MYCN. (日)
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| ○要約 (任意): | □ | (英) Overexpression of MYCN is a hallmark of neuroblastoma (NB). ALK(R1275Q), an activating mutation of ALK (anaplastic lymphoma kinase), has been found in sporadic and familial NB patients. In this report, we demonstrated that ALK(R1275Q) knock-in, MYCN transgenic compound mice developed NB with complete penetrance. Transcriptome analysis revealed that ALK(R1275Q) globally downregulated the expression of extracellular matrix (ECM)- and basement membrane (BM)-associated genes in both primary neuronal cells and NB tumors. Accordingly, ALK(R1275Q)/MYCN tumors exhibited reduced expression of ECM/BM-related proteins as compared with MYCN tumors. In addition, on MYCN transduction, ALK(R1275Q)-expressing neuronal cells exhibited increased migratory and invasive activities. Consistently, enhanced invasion and metastasis were demonstrated in ALK(R1275Q)/MYCN mice. These results collectively indicate that ALK(R1275Q) confers a malignant potential on neuronal cells that overexpress MYCN by impairing normal ECM/BM integrity and enhancing tumor growth and dissemination. Moreover, we found that crizotinib, an ALK inhibitor, almost completely inhibited the growth of ALK(R1275Q)/MYCN tumors in an allograft model. Our findings provided insights into the cooperative mechanism of the mutated ALK and overexpressed MYCN in the pathogenesis of NB and demonstrated the effectiveness of crizotinib on ALK(R1275Q)-positive tumors. (日)
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| ○キーワード (推奨): |
| ○発行所 (推奨): | □ | Nature Publishing Group
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| ○誌名 (必須): | □ | Oncogene ([Nature Publishing Group])
(pISSN: 0950-9232, eISSN: 1476-5594)
| ○ISSN (任意): | □ | 1476-5594
ISSN: 0950-9232
(pISSN: 0950-9232, eISSN: 1476-5594) Title: OncogeneTitle(ISO): OncogenePublisher: Springer Nature (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 35
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| ○号 (必須): | □ | 34
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| ○頁 (必須): | □ | 4447 4458
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2016年 8月 25日 (平成 28年 8月 25日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1038/onc.2015.519 (→Scopusで検索)
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| ○PMID (任意): | □ | 26829053 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1038/onc.2015.519 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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