Investigation of zinc transporters and signaling for development of anti-tumor drugs
| Project/Area Number |
17H04011
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 亜鉛シグナル / トランスポーター / シグナル伝達 / 悪性腫瘍 / 器官形成 / 創薬 / 亜鉛 / がん |
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| Outline of Final Research Achievements |
We have found that zinc transporter ZIP10 is essential for epithelial formation in mice, and its possible involvement in atopic dermatitis. We also demonstrated that ZIP14 is involved in pathophysiology of cancer cachexia. In addition, we found that zinc deficiency abrogates epigenetics that results in blocking the keratinocyte differentiation. Recently, we have developed the series of mice in which EGFP was inserted in promoter of several zinc transporters, which will be useful to investigate the roles of zinc signals in physiology and pathophysiology. We are currently investigating the involvement of each zinc transporters in cancers by using these mice.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性腫瘍における亜鉛シグナルの役割に焦点を当てて本研究を開始したが、研究段階で様々な発見がもたらされた。特に、亜鉛トランスポーターZIP10が毛包や表皮の形成に必須であること、アトピー性皮膚炎患者の患部ではその発現が減少していることについては、同様の研究領域からはもちろんのこと、一般からも多くの問い合わせを受けた。また、本研究によって、様々ながんにおける亜鉛トランスポーターの発現の精査の必要性が生じ、各種亜鉛トランスポーターのプロモーターにEGFPを挿入したマウスを作成した。当該マウスを用いることにより、皮膚がん等の様々ながんにおける亜鉛シグナルの役割解明と、創薬研究の進展が期待される。
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] The epithelial zinc transporter ZIP10 epigenetically regulates human epidermal homeostasis by modulating histone acetyltransferase activity2019
Author(s)
Bin BH, SH. Lee, J. Bhin, T. Irie, S. Kim, J. Seo, K. Mishima, TR. Lee, D. Hwang, T. Fukada, EG. Cho
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Journal Title
Br J Dermatol.
Volume: 180
Issue: 4
Pages: 869-880
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Generation of orthotopically functional salivary gland from embryonic stem cells2018
Author(s)
Tanaka Junichi、Ogawa Miho、Hojo Hironori、Kawashima Yusuke、Mabuchi Yo、Hata Kenji、Nakamura Shiro、Yasuhara Rika、Takamatsu Koki、Irie Tarou、Fukada Toshiyuki、Sakai Takayoshi、Inoue Tomio、Nishimura Riko、Ohara Osamu、Saito Ichiro、Ohba Shinsuke、Tsuji Takashi、Mishima Kenji
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Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 4216-4216
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle2018
Author(s)
Wang G, A. Biswas, W. Ma, M. Kandpal, C. Coker, P. Grandgenett, M. Hollingsworth, R Jain, K Tanji, S Lopez-Pintado, A. Borczuk, D. Hebert, S. Jenkitkasemwong, S. Hojyo, R. Davuluri, M. Knutson, T. Fukada, S. Acharyya
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Journal Title
Nature Medicine
Volume: 24
Issue: 6
Pages: 770-781
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] SLC39A14 deficiency alters manganese homeostasis and excretion resulting in brain manganese accumulation and motor deficits in mice2018
Author(s)
Jenkitkasemwong S, A. Akinyode, E. Paulus, R. Weiskirchen, S. Hojyo, T. Fukada, G. Giraldo, J. Schrier, A. Garcia, C. Janus, B. Giasson, M. Knutson
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 115
Issue: 8
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10-p63 axis in epithelial homeostasis.2017
Author(s)
1.Bin BH , Bhin J , Takaishia M , Toyoshima K , Kawamata S , Ito K , Hara T , Watanabe T , Irie T , Takagishi T, Lee SH , Jung HS, Rho S , Seo J , Choi DH, Hwang D , Koseki H , Ohara O , Sano S , Tsuji T , Mishima K , Fukada T.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 114
Issue: 46
Pages: 12243-12246
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-β expression.2017
Author(s)
Fukunaka A, Fukada T, Bhin J, Suzuki L, Tsuzuki T, Takamine Y, Bin BH, Yoshihara T, Ichinoseki-Sekine N, Naito H, Miyatsuka T, Takamiya S, Sasaki T, Inagaki T, Kitamura T, Kajimura S, Watada H, Fujitani Y.
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Journal Title
PLoS Genet.
Volume: 13(8)
Issue: 8
Pages: 1-23
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Requirement of Zinc Transporter SLC39A7/ZIP7 for Dermal Development to Fine-Tune Endoplasmic Reticulum Function by Regulating Protein Disulfide Isomerase.2017
Author(s)
Bin BH, J. Bhin, J. Seo, SY. Kim, E. Lee, K. Park, DH. Choi, T. Takagishi, T. Hara, D. Hwang, H. Koseki, Y. Asada, S. Shimoda, K. Mishima, T. Fukada.
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Journal Title
Journal of Investigative Dermatology
Volume: 137
Issue: 8
Pages: 1682-1691
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Book] Zinc Signaling2019
Author(s)
Toshiyuki Fukada*, Taiho Kambe* (*編集者)
Total Pages
413
Publisher
Springer Nature, Singapore
ISBN
9789811505577
Related Report
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