Roles of transcription factors role of transcription factors in the maintenance of endothelial identity
| Project/Area Number |
17K07157
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Niigata University (2019-2020)
Tokyo Medical and Dental University (2017-2018) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | がん関連線維芽細胞 / 血管 / 血管内皮細胞 / 間葉系細胞 / 内皮間葉移行 / TGF-β / Activin / Etsファミリー転写因子 / 炎症性サイトカイン / がん悪性化 / EndMT / Ets family 転写因子 / リンパ管内皮細胞 / 内皮細胞 / 内皮間葉移行（EndMT） / 転写因子 / 発現制御 |
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| Outline of Final Research Achievements |
A subset of fibroblasts, which are involved in the malignant progression of various diseases, differentiate from endothelial cells through a phenomenon called endothelial-mesenchymal transition. However, the role and molecular mechanism of the endothelial differentiation remain unclear. Therefore, we attempted to elucidate it in this study. Hypothesizing that transcription factors are necessary for endothelial cells to maintain their properties as endothelial cells without undergoing endothelial-mesenchymal transition, we identified an Ets family transcription factor that functions in blood vascular endothelial cells. We also found that a different Ets family transcription factor is important in lymphatic endothelial cells, which are a different type of endothelial cells. In addition, we were able to identify different endogenous cytokines as accelerators of endothelial-mesenchymal transition that are regulated by these transcription factors, respectively.
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| Academic Significance and Societal Importance of the Research Achievements |
今回解明されたEndMT抑制因子としてのEtsファミリー転写因子の役割から、内皮細胞から線維芽細胞へと分化する際には、Etsファミリーを含む複数の転写因子によってそれぞれの細胞マーカーの発現が制御を受けることが明らかになり、複雑な転写ネットワークが存在することが示唆された。腫瘍血管内皮細胞やがん関連線維芽細胞は特に正常のそれとは非常に異なる性質を持つことが知られており、腫瘍における特異な生命現象の理解に大きく貢献したと考えられる。さらに今回このEndMTに関与することが示された分子群は、がんにおける新たな標的分子や診断マーカーになる可能性があり、がんの分子標的治療の選択肢を広げた意義は大きい。
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Report
(5 results)
Research Products
(54 results)
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[Journal Article] ASK1 suppresses NK cell-mediated intravascular tumor cell clearance in lung metastasis.2021
Author(s)
Fujimoto, M., Kamiyama, M., Fuse, K., Ryuno, H., Odawara, T., Furukawa, N., Yoshimatsu, Y., Watabe, T., Michaela, P.-M., Veronika, S., Tahara, H., Hayakawa, Y., Sato, T., Takeda, K., Naguro, I. and Ichijo, H.
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Journal Title
Cancer Science
Volume: 112
Issue: 4
Pages: 1633-1643
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] TGF-β and TNF-α cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals2020
Author(s)
Yoshimatsu Y, Kimuro S, Pauty J, Takagaki K, Nomiyama S, Inagawa A, Maeda K, Podyma-InoueKA, Kajiya K, Matsunaga Y, Watabe T
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Journal Title
PLOS ONE
Volume: 15
Issue: 5
Pages: e0232356-e0232356
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] TNF-α enhances TGF-β-induced endothelial-to-mesenchymal transition via TGF-β signal augmentation2020
Author(s)
Yasuhiro Yoshimatsu, Ikumi Wakabayashi, Shiori Kimuro, Naoya Takahashi, Kazuki Takahashi, Miho Kobayashi, Nako Maishi, Katarzyna A. Podyma-Inoue, Kyoko Hida, Kohei Miyazono, Tetsuro Watabe
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Journal Title
Cancer Sciense
Volume: -
Issue: 7
Pages: 2385-2399
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fibroblast growth factor signals regulate transforming growth factor-β-induced endothelial-to-myofibroblast transition of tumor endothelial cells via Elk12019
Author(s)
Akatsu Y*, Takahashi N*, Yoshimatsu Y*, Kimuro S, Muramatsu T, Katsura A, Maishi N, Suzuki HI, Inazawa J, Hida K, Miyazono K, Watabe T. (＊equal contribution)
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Journal Title
Molecular Oncology
Volume: 13
Issue: 8
Pages: 1706-1724
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Interleukin-13 receptor α2 is a novel marker and potential therapeutic target for human melanoma.2019
Author(s)
Okamoto H*, Yoshimatsu Y*, Tomizawa T*, Kunita A*, Takayama R*, Morikawa T, Komura D, Takahashi K, Oshima T, Sato M, Komai M, Podyma-Inoue KA, Uchida H, Hamada H, Fujiu K, Ishikawa S, Fukayama M, Fukuhara T, Watabe T. (* equal contributor)
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Journal Title
Sci Rep.
Volume: 9
Issue: 1
Pages: 1281-1281
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] リンパ脈管筋腫症肺組織からのリンパ管内皮細胞の分離および特性分析2020
Author(s)
西野宏一, 吉松康裕, 関本康人, 岡本翔一, 村松智輝, 三谷恵子, 小林悦子, 江花弘基, 栗原正利,稲澤譲治, 高橋和久, 渡部徹郎, 瀬山邦明
Organizer
第44回日本リンパ学会総会
Related Report
Invited
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[Presentation] Oral squamous carcinoma cells under TGF-β-induced cell cycle arrest represent highly motile and invasive population2020
Author(s)
Katarzyna A. Inoue, Kazuki Takahashi, Maki Saito, Atsushi Kaida, Akinari Sugauchi, Toshihiro Uchihashi, Yasuhiro Yoshimatsu, Susumu Tanaka, Masahiko Miura, Mikihiko Kogo, Tetsuro Watabe.
Organizer
AACR Virtual Special Conference
Related Report
Int'l Joint Research
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[Book] リンパ学 第42巻，1号 「リンパ管内皮細胞における転写因子・シグナルネットワークの役割」2019
Author(s)
吉松康裕, 山崎智子, 赤津裕一, 原田香織, 三嶋弘一, 宮崎秀幹, 伊藤太智, 稲川諒彦, 紀室志織, 宮園浩平, 渡部徹郎.
Total Pages
4
Publisher
ライフメディコム
Related Report
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