Analysis of the molecular mechanism and clinical targets for neural tumors via the loss of function of NF1/NF2 gene products

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293312
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• 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)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: neurofibromatosis / NF1 / proteomics / mTOR / TCTP

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.

Free Research Field

腫瘍生化学