Analysis of the mechanism of tumorigenesis related to Neurofibromatosis type-1 and development of their therapeutic strategies targeting translation regulation by TCTP-EF1A2

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07691
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Niigata University
• Principal Investigator: Kobayashi Daiki 新潟大学, 医歯学系, 助教 (20448517)
• Co-Investigator(Kenkyū-buntansha): 荒木 令江 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 神経線維腫1型 / MPNST / TCTP / EF1A2 / クロスリンク質量分析

Outline of Final Research Achievements

Previous studies have demonstrated that the expression of translationally regulated tumor protein (TCTP) is elevated in neurofibromatosis type 1 (NF1) tumor cells and that TCTP contributes to NF1 tumor malignancy through its interaction with a group of translation elongation factors, mainly EF1A2. In this study, the binding sites of TCTP- and EF1A2-interacting proteins were analyzed by crosslinking mass spectrometry. As a result, it has been found that the binding site of TCTP to EF1A2 is located near the binding site of EF1A2 and its activators. Based on these information, it has been expected that therapies using selective drugs that inhibit the binding of TCTP to a group of NF1 tumor-specific translation elongation factors have been developed.

Free Research Field

プロテオミクス

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、TCTP-EF1A2を介した神経線維腫症1型（NF1）腫瘍の悪性化メカニズムの理解を深めることに成功し、これらの情報を基にTCTPとEF12Aを中心としたNF1腫瘍特異的な翻訳伸長因子群の結合を阻害する薬剤をスクリーニングすることによって、NF1腫瘍のより効果的な治療法の開発が期待される。したがって本研究成果は、NF1腫瘍のメカニズム解明と治療法の開発に向けた重要な一歩であり、学術的にも社会的にも大きな意義を持つと考えられる。