Development of recurrence mouse brain tumor model using inducible iCSCs and identification of target molecules in recurrence tumor

• Project/Area Number: 25830088
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Keio University
• Principal Investigator: ONISHI NOBUYUKI 慶應義塾大学, 医学部, 特任助教 (40534540)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経幹細胞 / ＡＬＫキナーゼ / 脳腫瘍モデル / ALKキナーセ / ALKキナーゼ

Outline of Final Research Achievements

The cancer stem cells (CSCs) are thought that the cause of local recurrence or distant organ metastasis following therapy. In this study, we have established the inducible mouse brain tumor model transplanting the genetically modified neural stem cells (NSCs) using Tet-On system. Inducible expression of activated-ALK could transform the NSCs in the presence of Dox treatment in mice. Next, we performed the exome sequence analysis to investigate the genetic aberration in the activated-ALK or -H-RAS expressing NSCs. Exome data showed that characteristic change of copy number in each chromosomes were observed in these cells. Using the inducible mouse brain tumor model, we would like to establish the recurrence mouse brain tumor model and identify the target molecules in recurrence tumors by analyzing copy number change.

Research Products

• [Journal Article] IGF2 Preserves Osteosarcoma Cell Survival by Creating an Autophagic State of Dormancy That Protects Cells against Chemotherapeutic Stress (2014)
  • Author(s): Shimizu T, Sugihara E, Yamaguchi-Iwai S, Tamaki S, Koyama Y, Kamel W, Ueki A, Ishikawa T, Chiyoda T, Osuka S, Onishi N, Ikeda H, Kamei J, Matsuo K, Fukuchi Y, Nagai T, Toguchida J, Toyama Y, Muto A, Saya H
  • Journal Title: Cancer Res Volume: 74 Issue: 22 Pages: 6531-6541
  • DOI: 10.1158/0008-5472.can-14-0914
  • Peer Reviewed
• [Journal Article] Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation. (2014)
  • Author(s): Nobusue H
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 3368-3368
  • DOI: 10.1038/ncomms4368
  • Peer Reviewed
• [Journal Article] IGF1 receptor signaling regulates adaptive radioprotection in glioma stemcells (2013)
  • Author(s): Osuka S. Sampetrean O, Shimizu T, Saga l, Onishi N, Sugihara E, Okubo J, Fujita S, Takano S, Matsumura A, Saya H
  • Journal Title: Stem Cells Volume: 31 Issue: 4 Pages: 627-640
  • DOI: 10.1002/stem.1328
  • Peer Reviewed
• [Journal Article] Twist2 functions as a tumor suppressor in murine osteosarcoma cells. (2013)
  • Author(s): Ishikawa T, Shimizu T, Ueki A, Yamaguchi S, Onishi N, Sugihara E, Kuninaka S, Miyamoto T, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Mabuchi Y, Matsuzaki Y, Yamaguchi R, Miyano S and Saya H
  • Journal Title: Cancer Sci Volume: (in press) Issue: 7 Pages: 880-888
  • DOI: 10.1111/cas.12163
  • Peer Reviewed
• [Journal Article] Targeting Aurora B to the equatorial cortex by MKlp2 is required for cytokinesis. (2013)
  • Author(s): Kitagawa M, Fung SY, Onishi N, Saya H, Lee SH.
  • Journal Title: PLoS One. Volume: 8 Issue: 6 Pages: e64826-e64826
  • DOI: 10.1371/journal.pone.0064826
  • Peer Reviewed
• [Journal Article] Acquired expression of NFATc1 downregulates E-cadherin and promotes cancer cell invasion. (2013)
  • Author(s): Oikawa T
  • Journal Title: Cancer Res Volume: 73 Issue: 16 Pages: 5100-5109
  • DOI: 10.1158/0008-5472.can-13-0274
  • Peer Reviewed
• [Presentation] Oncogenic stressをバイパスするALK発がんシグナルの解析 (2015)
  • Author(s): 大西 伸幸、滝田 順子、小川 誠司、佐谷 秀行
  • Organizer: 日本癌学会シンポジウム・共同利用共同研究拠点シンポジウム
  • Place of Presentation: 石川県立音楽堂交流ホール (金沢市)
  • Year and Date: 2015-01-21 – 2015-01-22
• [Presentation] Development and analysis of mouse brain tumor models derived from neural stem cells expressing activated ALK (2014)
  • Author(s): Nobuyuki Onishi, Oltea Sampetrean, Eiji Sugihara, Hideyuki Saya.
  • Organizer: American Association for Cancer Research Annual Meeting 2014
  • Place of Presentation: SAN DIEGO Convention Center （the US)
  • Year and Date: 2014-04-05 – 2014-04-11
• [Presentation] Development and analysis of mouse brain tumor models derived from neural stem cells expressing activated ALK (2014)
  • Author(s): Nobuyuki Onishi, Teppei Shimamura, Yasunobu Nagata, Junko Takita, Satoru Miyano, Seishi Ogawa, Hideyuki Saya
  • Organizer: International Symposium on Tumor Biology in Kanazawa & Symposium on Drug Discovery in Academics
  • Place of Presentation: Kanazawa
• [Presentation] 神経幹細胞を用いたALK 発がんモデルの構築ならびに解析
  • Author(s): 大西 伸幸，島村 徹平，永田 安伸，滝田 順子，宮野 悟，小川 誠司，佐谷 秀行
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Remarks] アクチン細胞骨格の動態が脂肪分化を誘導するメカニズムを解明
  • URL: http://www.jst.go.jp/pr/announce/20140226/