| ○種別 (必須): | □ | 学術論文 (審査論文)
| [継承] |
| ○言語 (必須): | □ | 英語
| [継承] |
| ○招待 (推奨): |
| ○審査 (推奨): | □ | Peer Review
| [継承] |
| ○カテゴリ (推奨): | □ | 研究
| [継承] |
| ○共著種別 (推奨): | □ | 国内共著 (徳島大学内研究者と国内(学外)研究者との共同研究 (国外研究者を含まない))
| [継承] |
| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Nakatsuka T (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 2. | (英) Tateishi K (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 3. | (英) Kudo Y (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 4. | (英) Yamamoto K (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 5. | (英) Nakagawa H (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 6. | (英) Fujiwara H (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 7. | (英) Takahashi R (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 8. | (英) Miyabayashi K (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 9. | (英) Asaoka Y (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 10. | (英) Tanaka Y (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 11. | (英) Ijichi H (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 12. | (英) Hirata Y (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 13. | (英) Otsuka M (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 14. | (英) Kato M (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 15. | (英) Sakai J (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 16. | 立花 誠
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 17. | (英) Aburatani H (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 18. | (英) Shinkai Y (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 19. | (英) Koike K (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| ○題名 (必須): | □ | (英) Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation. (日)
| [継承] |
| ○副題 (任意): |
| ○要約 (任意): | □ | (英) Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation. Particularly, the expression of Cd44, a liver cancer stem marker, was regulated by AP-1 in a Kdm3a-dependent manner. We identified Cd44-positive hepatocytes with epithelial-mesenchymal transition-related expression profiles in the Pik3ca Tg liver and confirmed their in vivo tumorigenic capacity. Notably, the number and tumor-initiating capacity of Cd44-positive hepatocytes were governed by Kdm3a. As a mechanism in Kdm3a-dependent AP-1 transcription, Kdm3a recruited c-Jun to the AP-1 binding sites of Cd44, Mmp7 and Pdgfrb without affecting c-Jun expression. Moreover, Brg1, a component of the SWI/SNF chromatin remodeling complex, interacted with c-Jun in a Kdm3a-dependent manner and was bound to the AP-1 binding site of these genes. Finally, KDM3A and c-JUN were co-expressed in 33% of human premalignant lesions with PI3K activation. Our data suggest a critical role for KDM3A in the PI3K/AP-1 oncogenic axis and propose a novel strategy for inhibition of KDM3A against liver tumor development under PI3K pathway activation.Oncogene advance online publication, 10 July 2017; doi:10.1038/onc.2017.222. (日)
| [継承] |
| ○キーワード (推奨): | 1. | (英) Animals (日) (読)
| [継承] |
| 2. | 発癌 (carcinogenesis)
| [継承] |
| 3. | (英) Carcinoma, Hepatocellular (日) (読)
| [継承] |
| 4. | (英) Cell Line, Tumor (日) (読)
| [継承] |
| 5. | (英) Class I Phosphatidylinositol 3-Kinases (日) (読)
| [継承] |
| 6. | (英) Epigenesis, Genetic (日) (読)
| [継承] |
| 7. | (英) Humans (日) (読)
| [継承] |
| 8. | (英) Jumonji Domain-Containing Histone Demethylases (日) (読)
| [継承] |
| 9. | (英) Liver Neoplasms (日) (読)
| [継承] |
| 10. | (英) Liver Neoplasms, Experimental (日) (読)
| [継承] |
| 11. | (英) Male (日) (読)
| [継承] |
| 12. | (英) Mice (日) (読)
| [継承] |
| 13. | ノックアウトマウス (knockout mice)
| [継承] |
| 14. | (英) Mice, Transgenic (日) (読)
| [継承] |
| 15. | (英) Phosphatidylinositol 3-Kinases (日) (読)
| [継承] |
| 16. | (英) Phosphorylation (日) (読)
| [継承] |
| 17. | シグナル伝達 (signal transduction)
| [継承] |
| 18. | (英) Transcription Factor AP-1 (日) (読)
| [継承] |
| ○発行所 (推奨): |
| ○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] |
| [継承] |
| ○巻 (必須): | □ | 36
| [継承] |
| ○号 (必須): | □ | 45
| [継承] |
| ○頁 (必須): | □ | 6262 6271
| [継承] |
| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2017年 12月 末日 (平成 29年 12月 末日)
| [継承] |
| ○URL (任意): |
| ○DOI (任意): | □ | 10.1038/onc.2017.222 (→Scopusで検索)
| [継承] |
| ○PMID (任意): | □ | 28692045 (→Scopusで検索)
| [継承] |
| ○CRID (任意): |
| ○Scopus (任意): | 1. | 2-s2.0-85033477641
| [継承] |
| ○researchmap (任意): |
| ○評価値 (任意): |
| ○被引用数 (任意): |
| ○指導教員 (推奨): |
| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1038/onc.2017.222 (日)
| [継承] |
| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
| [継承] |