Elucidation of the pathogenic mechanism of, and construction of therapeutic strategy for, Neurofibromatosis type 1-associated tumors via TCTP

2013 Fiscal Year Final Research Report

• Project/Area Number: 24700981
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kumamoto University
• Principal Investigator: KOBAYASHI Daiki 熊本大学, 生命科学研究部, 研究員 (20448517)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 神経線維腫 / NF1 / TCTP / Neurofibromin / プロテオミクス

Research Abstract

Neurofibromatosis type-1 (NF1) is an inherited disorder that presents various pathological conditions including benign neurofibromas and malignant tumors. Due to the lack of information on the molecular mechanism of NF1-associated tumor pathogenesis or biomarkers/therapeutic targets, a radical treatment for NF1 tumors has not been established. In this study, we evaluated whether the novel NF1-associated protein, translationally controlled tumor protein (TCTP), could be a novel biomarker and therapeutic target for NF1-associated tumors. We found that TCTP expression level correlated with their malignancy and contributes to NF1-associated tumor cell growth. Collective to our findings, it is expected that a diagnostic method and therapeutic strategies targeting TCTP for NF1-associated tumors has been developed.

Research Products

• [Journal Article] Integrated proteomics identified a novel activation signaling of dynein IC2-GR-COX-1 in NF1 disease model cells (2013)
  • Author(s): Hirayama M, Kobayashi D, Mizuguchi S, Morikawa T, Nagayama M, Midorikawa U, Wilson MM, Nambu AN, Yoshizawa A, Kawano S, and Araki N
  • Journal Title: Molecular & Cellular Proteomics Volume: 12 Pages: 1377-1394
  • DOI: 10.1074/mcp.M112.024802
  • Peer Reviewed
• [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, Nagayama M, Hirayama M, Kobayashi D, Tsubota N, Takezaki T, Makino K, Nakamura H, Takeya M, Kuratsu J and Araki N
  • Journal Title: PLOS ONE Volume: 21 Pages: e59558
  • DOI: 10.1371/journal.pone.0059558
• [Presentation] 融合プロテオミクスによる新規神経線維腫症1型(NF1)関連因子TCTPの同定と、そのNF1腫瘍における機能解析 (2012)
  • Author(s): 小林大樹、平山未央、菰原義弘、水口惣平、ウィルソン森藤政代、尹浩信、竹屋元裕、倉持朗、荒木令江
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 福岡国際会議場、福岡市
  • Year and Date: 2012-12-15
• [Presentation] Integrated Proteomics Identified Translationally Controlled Tumor Protein as a Biological Target for Neurofibroma and Malignant Peripheral Nerve Sheath Tumors (2012)
  • Author(s): Kobayashi D, Hirayama M, Komohara Y, Mizuguchi S, Wilson-morifuji M, Ihn h, Takeya M, Kuramochi A, Araki N
  • Organizer: HUPO 11th Annual World Congress
  • Place of Presentation: Hynes Covention Center. Boston, US
  • Year and Date: 2012-09-10
• [Presentation] 融合プロテオミクスによる新規神経線維腫症I型(NF1)関連因子TCTPの同定と、治療標的としての機能解析 (2012)
  • Author(s): 小林大樹、平山未央、菰原義弘、水口惣平、ウィルソン-森藤政代、尹浩信、竹屋元裕、倉持朗、荒木令江
  • Organizer: 日本プロテオーム学会2012年大会日本ヒトプロテオーム機構
  • Place of Presentation: 日本科学未来館、東京都
  • Year and Date: 2012-07-27
• [Book] 皮膚科臨床アセット15母斑と母斑症『神経線維腫症2型』 (2013)
  • Author(s): 荒木令江, 南部晶子, 小林大樹
  • Total Pages: 181-189
  • Publisher: 中山書店
• [Patent(Industrial Property Rights)] 融合プロテオミクスによるNF1特異的タンパク質の同定方法、NF1特異的タンパク質発現抑制方法、NF1特異的タンパク質の腫瘍マーカー及び治療ターゲットとしての使用方法 (2012)
  • Inventor(s): 荒木令江、小 林大樹、水口惣平、平山未央
  • Industrial Property Rights Holder: 国立大学法人熊本大学
  • Industrial Property Rights Type: 特許特開2012-213391
  • Patent Publication Number: 特開2012-213391
  • Filing Date: 2012-11-08
• [Patent(Industrial Property Rights)] 統合プロテオミクス解析用データ群の生成方法並びに同生成方法にて生成した統合プロテオミクス解析用データ群を用いる統合プロテオミクス解析方法、およびそれを用いた原因物質同定方法 (2012)
  • Inventor(s): 荒木令江、水口惣平、森川崇、坪田誠之、小林大樹、倉津純一、ウイルソン政代
  • Industrial Property Rights Holder: 国立大学法人熊本大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2012-509621
  • Filing Date: 2012-09-11