Analysis of the molecular mechanism and clinical targets for neural tumors via the loss of function of NF1/NF2 gene products
Project/Area Number |
25293312
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Neurosurgery
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Research Institution | Kumamoto University |
Principal Investigator |
Araki Norie 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722)
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Co-Investigator(Kenkyū-buntansha) |
KURATSU Junichi 熊本大学, 大学院生命科学研究部, 教授 (20145296)
NAKAMURA Hideo 熊本大学, 付属病院, 講師 (30359963)
小林 大樹 熊本大学, 大学院生命科学研究部, 産学関連系研究員 (20448517)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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Keywords | neurofibromatosis / NF1 / proteomics / mTOR / TCTP / 神経線維腫症 / NF2 / プロテオミクス / トランスクリプトーム / 融合プロテオミクス / 脳神経系腫瘍 |
Outline of Final Research Achievements |
Neurofibromatosis type 1/2 (NF1/2) is an autosomal dominant disease that predisposes individuals to develop neural tumors including neurofibromas and malignant tumors etc. To identify novel biological targets for NF-associated tumors, a unique integrated-omics was performed, and a novel abnormal network, “Translationally controlled tumor protein (TCTP)-mTOR/EF signalings” was identified. This network activates the MAPK/PI3K-AKT-mTOR and specific EF1 complex associated translational signalings in NF1 tumors. In NF1-deficient MPNST cells, MAPK/PI3K/mTOR inhibitors downregulated TCTP associated cell expansions, and TCTP knockdown (or overexpression) suppressed (or activated) mTOR/EF1 signalings. Artesunate, a TCTP target, inhibited the TCTP-mTOR/EF1 signal cascade and suppressed the viability of MPNST cells significantly. These findings suggest that TCTP-mTOR/EF signaling is implicated in the progression of NF1-tumors and could serve as a biological target for the specific therapy.
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Report
(4 results)
Research Products
(89 results)
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[Journal Article] CXCL12/CXCR4 Activation by Cancer-Associated Fibroblasts Promotes Integrin ß1 Clustering and Invasiveness in Gastric Cancer.2016
Author(s)
Izumi D, Ishimoto T, Miyake K, Sugihara H, Eto K, Sawayama H, Yasuda T, Kiyozumi Y, Kaida T, Kurashige J, Imamura Y, Hiyoshi Y, Iwatsuki M, Iwagami S, Baba Y, Sakamoto Y, Miyamoto Y, Yoshida N, Watanabe M, Takamori H, Araki N, et al
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Journal Title
Int J Cancer.
Volume: 138(5)
Pages: 1207-1219
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Development of a fully automated two dimensional electrophoresis device, Auto-2D, and its clinical applications. Proteome Letters, 2016 in press2016
Author(s)
Araki N, Goto S, Matsunaga T, Kinoshita H, Nishimura M, Midorikawa U, Kobayashi D, Yabe K.
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Journal Title
Proteome Letters
Volume: 印刷中
Pages: 印刷中
Related Report
Open Access
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[Journal Article] Translationally Controlled Tumor Protein is a Novel Biological Target for Neurofibromatosis Type 1 (NF1)-associated Tumors.2014
Author(s)
Kobayashi, D., Hirayama M., Komohara, Y., Mizuguchi, S, Wilson Morifuji, M. Patrakitkomjorn, S, Ihn, H., Takeya, M, Kuramochi, A., and Araki, N*.
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Journal Title
J. Biol. Chem.
Volume: 289(38)
Pages: 26314-26
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Glioma initiating cells form a differentiation niche via the induction of extracellular matrices and integrinαV.2013
Author(s)
Nambu, NA., Midorikawa U, Mizuguchi S, Hide T, Nagai M, Komohara Y, Nagayama1 M, Hirayama M, Kobayashi D, Tsubota N, Takezaki T, Makino K, Nakamura H, Takeya M, Kuratsu J and Araki N*.
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Journal Title
PLOS ONE
Volume: 8(5)
Pages: e59558
DOI
Related Report
Peer Reviewed
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[Journal Article] Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a-receptor (CD88).2013
Author(s)
Nitta H, Wada Y, Kawano Y, Murakami Y, Irie A, Taniguchi K, Kikuchi K, Yamada G, Suzuki K, Honda J, Wilson MM, Araki N, Eto M, Baba H and Imamura T.
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Journal Title
Clinical Cancer Research
Volume: 19(8)
Pages: 19(8)
DOI
Related Report
Peer Reviewed
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[Journal Article] CA-S27: A novel Lewis A associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma.2013
Author(s)
Silsirivanit A, Araki N*, Wongkham C, Vaeteewoottacharn K, Pairojkul C, Kuwahara K, Narimatsu Y, Sawaki H, Narimatsu H, Okada S, Sakaguchi N, Wongkham S*
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Journal Title
Cancer Sci.
Volume: 104(10)
Pages: 1278-84
DOI
Related Report
Peer Reviewed
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[Journal Article] Integrated View of the Human Chromosome X-centric Proteome Project.2013
Author(s)
Yamamoto T, Nakayama K, Hirano H, Tomonaga T, Ishihama Y, Yamada T, Kondo T, Kodera Y, Sato Y, Araki N, Mamitsuka H, Goshima N.
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Journal Title
J Proteome Res.
Volume: 12
Pages: 58-61
DOI
Related Report
Peer Reviewed
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[Journal Article] Epiplakin modifies the motility of the HeLa cells and accumulates at the outer surfaces of three-dimensional cell clusters.2013
Author(s)
Shimada, H; Nambu-Niibori, A; Wilson-Morifuji, M; Mizuguchi, S; Araki, N; Mezaki, Y; Senoo, H; Ishikawa, K; Okamoto, O; Fujiwara, S.
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Journal Title
J. Dermatol.
Volume: 40(4)
Pages: 249-58
DOI
Related Report
Peer Reviewed
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[Journal Article] Renal Denervation Prevents Stroke and Brain Injury via Attenuation of Oxidative Stress in Hypertensive Rats2013
Author(s)
Nakagawa T, Hasegawa Y, Uekawa K, Ma M, Katayama T, Sueta D, Toyama K, Kataoka K, Koibuchi N, Maeda M, Kuratsu JI, Kim-Mitsuyama S.
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Journal Title
J Am Heart Assoc
Volume: 2(5)
Pages: e000375
DOI
Related Report
Peer Reviewed
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[Journal Article] Discovery of an uncovered region in fibrin clots and its clinical significance.2013
Author(s)
Hisada Y, Yasunaga M, Hanaoka S, Saijou S, Sugino T, Tsuji A, Saga T, Tsumoto K, Manabe S, Kuroda J, Kuratsu J, Matsumura Y.
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Journal Title
Sci Rep
Volume: 3
Pages: 2604.
DOI
Related Report
Peer Reviewed
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[Journal Article] Pretreatment with rosuvastatin protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress and inflammation2013
Author(s)
Ma M, Uekawa K, Hasegawa Y, Nakagawa T, Katayama T, Sueta D, Toyama K, Kataoka K, Koibuchi N, Kuratsu J, Kim-Mitsuyama S.
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Journal Title
Brain Res.
Volume: 1519
Pages: 87-94
DOI
Related Report
Peer Reviewed
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[Journal Article] TGF-β mediates homing of bone marrow-derived human mesenchymal stem cells to glioma stem cells2013
Author(s)
Shinojima N, Hossain A, Takezaki T, Fueyo J, Gumin J, Gao F, Nwajei F, Marini FC, Andreeff M, Kuratsu J, Lang FF.
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Journal Title
Cancer Res.
Volume: 73(7)
Pages: 2333-44.
DOI
Related Report
Peer Reviewed
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[Presentation] jPOST: Development of Japan ProteOme STandard Repository/Database2015
Author(s)
Shin Kawano , Yuki Moriya , Shujiro Okuda , Tadashi Yamamoto , Masaki Matsumoto , Daiki Kobayashi, Norie Araki, Akiyasu C. Yoshizawa, Tsuyoshi Tabata, Naoyuki Sugiyama, Susumu Goto, Yasushi Ishihama
Organizer
HUPO2015
Place of Presentation
Vancouver Convention Centre (Canada)
Year and Date
2015-09-27 – 2015-09-30
Related Report
Int'l Joint Research
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[Presentation] Functional analysis of chloroquine toxicity2015
Author(s)
Diwakar Guragain , Atit Silsirivanit , Wunchana Seubwai , Sopit Wongkham , Ubon Cha’on , Akira Sasao , Ako Sasao , Norie Araki
Organizer
日本プロテオーム学会2015年会
Place of Presentation
熊本森都市プラザ(熊本)
Year and Date
2015-07-22 – 2015-07-23
Related Report
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[Presentation] Integrated Proteomics for Cancer Stem Cells2014
Author(s)
Norie Araki, Akiko Nambu, Uichi Midorikawa, Souhei Mizuguchi, Daiki Kobayashi, Jun-ichi Kuratsu
Organizer
13th human proteome organization World Congress
Place of Presentation
IFEMA Madrid Spain
Year and Date
2014-10-05 – 2014-10-08
Related Report
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[Presentation] An Integrated Proteomics for Extracting Molecular Target of Malignant Gliomas.2013
Author(s)
Norie Araki, Takashi Morikawa, Souhei Mizuguchi, Daiki Kobayashi, Akiko Niibori Nambu, Uichi Midorikawa, Mio Hirayama, Masayo morifuji Wilson, Sin Kawano, Hideo Nakamura, Junichi Kuratsu.
Organizer
HUPO 11th Annual World Congress
Place of Presentation
パシフィコ横浜
Year and Date
20130914-20130918
Related Report
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[Presentation] Integrated Proteomics Identified Novel Activation of Dynein IC2-GR-COX-1 Signaling by Suppression of NF1 Tumor Suppressor Gene Product, Neurofibromin, in Neuronal Cells..2013
Author(s)
Daiki Kobayashi, Mio Hirayama, Souhei Mizuguchi Takashi Morikawa, Megumi Nagayama, Uichi Midorikawa, Masayo Wilbu-Niibori, Akiyasu Yoshizawa C., Shin Kawano, Norie Araki.
Organizer
HUPO 11th Annual World Congress
Place of Presentation
パシフィコ横浜
Year and Date
20130914-20130918
Related Report
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[Presentation] Integrated Proteomics Identified the Akiko Differentination Niche Induced by glioma Stem Cells.2013
Author(s)
Niiboari Nambu, Uichi Midorikawa, Souhei Mizuguchi, Takuichiro Hide, Minako Nagai, Yoshihiro Komohara, Megumi Nagayama, Mio Hirayama, Daiki Kobayashi, Hideo Nakamura, Motohiro Takeya, Jyunichi Kuratsu, Norie Araki.
Organizer
HUPO 11th Annual World Congress
Place of Presentation
パシフィコ横浜
Year and Date
20130914-20130918
Related Report
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[Presentation] A quick profiling System for Cancer marker Proteins with Diverse Post-Translational Modifications by a Fully Automated 2DE Device, Auto-2D2013
Author(s)
Munenori Nishimura, Uichi Midorikawa, Megumi Nagayama, Daiki Kobayashi, Mio Hirayama, Yoji Murakami, Yoshihiro Wada, Takahisa Imamura, Yutaka Unuma, Norie Araki.
Organizer
HUPO 11th Annual World Congress
Place of Presentation
パシフィコ横浜
Year and Date
20130914-20130918
Related Report
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