Mechanism of NLRR1-regulated signaling pathway and establishment of a novel targeted therapy

• Project/Area Number: 22791016
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: TAKATORI Atsushi 千葉県がんセンター(研究所), 小児がん研究センター, 研究員 (40455390)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 小児腫瘍学 / 癌 / シグナル伝達 / NLRR / ノックアウトマウス

Research Abstract

New and efficient therapeutic strategies are required to improve overall survival for the high-risk neuroblastoma (NB). In the present project, intensive functional analyses have been performed to understand the mechanism of NLRR1-regulated growth signaling pathway. The study demonstrated that NLRR1 enhances proliferative signals rather than differentiating signals through membrane structure of lipid rafts. Functional screening has identified anti-NLRR1 monoclonal antibody harboring growth inhibitory effect, suggesting that a potential therapeutic strategy for NB therapy.

Research Products

• [Journal Article] NLRR1 enhances EGF-mediated MYCN induction in neuroblastoma and accelerates tumor growth in vivo. (2012)
  • Author(s): Hossain S
  • Journal Title: Cancer Res Volume: 72 Issue: 17 Pages: 4587-4596
  • DOI: 10.1158/0008-5472.can-12-0943
  • Peer Reviewed
• [Journal Article] Expression of NLRR3 orphan receptor gene is negatively regulated by MYCN and Miz-1, and its down-regulation is associated with unfavorable outcome in neuroblastoma (2011)
  • Author(s): Akter J, Takatori A, Hossain S, Ozaki T, Nakazawa A, Ohira M, Suenaga Y, Nakagawara A
  • Journal Title: Clin Cancer Res Volume: 17 Issue: 21 Pages: 6681-6692
  • DOI: 10.1158/1078-0432.ccr-11-0313
  • Peer Reviewed
• [Journal Article] The Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for evelid closure (2011)
  • Author(s): Geh E., Takatori A., 等
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Issue: 42 Pages: 17349-17354
  • DOI: 10.1073/pnas.1102297108
  • Peer Reviewed
• [Presentation] NLRR1, a direct target of MYCN, regulates cell growth both in vitro and in vivo and can be a therapeutic target against high-risk neuroblastoma (2012)
  • Author(s): Takatori, A.
  • Organizer: STOP2012
  • Place of Presentation: イギリス・ロンドン
  • Year and Date: 2012-10-07
• [Presentation] NLRR1によるEGFおよびIGFシグナルの制御メカニズムと新規分子標的治療法の可能性 (2012)
  • Author(s): 高取敦志他
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] NLRR1, a direct target of MYCN, regulates cell growth both in vitro and in vivo and can be a therapeutic target against high-risk neuroblastoma (2012)
  • Author(s): Takatori, A.
  • Organizer: Advanced Neuroblastoma Research (ANR) 2012
  • Place of Presentation: カナダ・トロント
  • Year and Date: 2012-06-19
• [Presentation] NLRR1, a direct target of MYCN, regulates cell growth both in vitro and in vivo and can be a therapeutic target against high-risk neuroblastoma (2012)
  • Author(s): Atsushi Takatori 等
  • Organizer: Advanced Neuroblastoma Research (ANR) 2012
  • Place of Presentation: フェアモント・ロイヤル・ヨーク（カナダ・トロント）
• [Presentation] NLRR1によるEGFおよびIGFシグナルの制御メカニズムと新規分子標的治療法の可能性 (2012)
  • Author(s): 高取 敦志 等
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] NLRR1, a direct target of MYCN, regulates cell growth both in vitro and in vivo and can be a therapeutic target against high-risk neuroblastoma (2012)
  • Author(s): Atsushi Takatori 等
  • Organizer: SIOP2012
  • Place of Presentation: バービカン・センター（イギリス・ロンドン）
  • Invited
• [Presentation] 増殖シグナルを制御するNLRR1を標的とした進行神経芽腫に対する治療用単クローン抗体の開発 (2012)
  • Author(s): 高取 敦志 等
  • Organizer: 第54回日本小児血液・がん学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] NLRR1, apotential molecular target of neuroblastoma, has functional significance in cell growth and mouse development (2011)
  • Author(s): 高取敦志他
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] NLRR1, a potential molecular target of neuroblastoma, has functional significance in cell growth and mouse development (2011)
  • Author(s): 高取敦志, 等
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-05
• [Presentation] NLRR1 enhances EGF and IGF signals through the components of lipid rafts and contributes to cell growth (2010)
  • Author(s): 高取、Hossain, 他4名
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-23
• [Presentation] 新規オーファン受容体NLRR1はEGFおよびIGFの増殖シグナルを増強する (2010)
  • Author(s): 高取、Hossain, 他4名
  • Organizer: 第19回日本癌病態治療研究会
  • Place of Presentation: 東京ステーションコンファレンス
  • Year and Date: 2010-06-30
• [Presentation] NLRR1, a direct target gene of MYCN, modulates aggressive growth of neuroblastoma by selectively enhancing EGF and IGF signals through the components of lipid rafts (2010)
  • Author(s): Takatori, A.
  • Organizer: ANR2010
  • Place of Presentation: スウェーデン・ストックホルム
  • Year and Date: 2010-06-22
• [Presentation] NLRR family proteins play distinct roles in deciding cell fate and affect the clinical outcome in neuroblastomas (2010)
  • Author(s): 高取、Hossain, 他7名
  • Organizer: 第101回アメリカ癌学会総会
  • Place of Presentation: アメリカ・デンバー
  • Year and Date: 2010-04-21