| 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 |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Kumamoto University |
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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 |
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| 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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