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Single cell screening of molecular target in using malignant neuroblastoma animal model

Research Project

Project/Area Number 16K10051
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionResearch Institute for Clinical Oncology, Saitama Cancer Center

Principal Investigator

Takenobu Hisanori  埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 研究員 (60392247)

Co-Investigator(Kenkyū-buntansha) 上條 岳彦  埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 所長 (90262708)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords幹細胞 / 発がん / 細胞分化 / トランスジェニック動物 / 小児腫瘍学
Outline of Final Research Achievements

Stem cell marker CD133 was upregulated in neuroblastoma (NB) sphere. CDX1 was identified as a transcription factor that directly induced CD133 expression in NB spheres by analysis of CD133 promoter region. CDX1 upregulated stem cell-related genes in NB cells. On the other hand, CDX1 suppressed tumor-related proliferation pathways. Then we generated CD133 and CDX1 conditional transgenic mice. These mice expressed transgenes in neural crest originated tissues.

Academic Significance and Societal Importance of the Research Achievements

神経芽腫を始めとした小児がんは、成人のがんと異なって遺伝子の変異を伴わずに発生する。したがって、発がんには何らかの遺伝子の発現異常が生じていると考えられるが、その分子機構はほとんど明らかになっていない。本研究で見出したCDX1は、神経芽腫のがん幹細胞に発現している転写因子であり、CD133をはじめとした幹細胞関連遺伝子の発現を上昇させることから、発がんだけでなく、複数の組織幹細胞の維持に関わっているものと考えられる。本課題で作出したCDX1のTgマウスは、発がんだけでなく、神経堤由来の組織の発生メカニズムを明らかにする、非常に有用なモデルとなりうる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (29 results)

All 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (27 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Journal Article] EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications2018

    • Author(s)
      Li Zhenghao、Takenobu Hisanori、Setyawati Amallia Nuggetsiana、Akita Nobuhiro、Haruta Masayuki、Satoh Shunpei、Shinno Yoshitaka、Chikaraishi Koji、Mukae Kyosuke、Akter Jesmin、Sugino Ryuichi P.、Nakazawa Atsuko、Nakagawara Akira、Aburatani Hiroyuki、Ohira Miki、Kamijo Takehiko
    • Journal Title

      Oncogene

      Volume: 37 Issue: 20 Pages: 2714-2727

    • DOI

      10.1038/s41388-018-0133-3

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CFC1 is a cancer stemness-regulating factor in neuroblastoma2017

    • Author(s)
      Chikaraishi Koji、Takenobu Hisanori、Sugino Ryuichi P.、Mukae Kyosuke、Akter Jesmin、Haruta Masayuki、Kurosumi Masafumi、Endo Takaho A.、Koseki Haruhiko、Shimojo Naoki、Ohira Miki、Kamijo Takehiko
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 28 Pages: 45046-45059

    • DOI

      10.18632/oncotarget.18464

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Reevaluation of PDGFRα signal in neuroblastoma: high expression and a new nonsynonymous mutation2018

    • Author(s)
      Shunpei Satoh, Miki Ohira, Hisanori Takenobu, Akira Nakagawara, Takehiko Kamijo
    • Organizer
      Advanced Neuroblastoma Research 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CDX1 regulates neuroblastoma stemness through MYC pathway modulation and reprogramming gene activation2018

    • Author(s)
      Hisanori Takenobu, Miki Ohira, Ryuichi Sugino, Koji Chikaraishi, Kyosuke Mukae, Nobuhiro Akita, Masayuki Haruta, Akira Nakagawara, Manabu Nakayama, Haruhiko Koseki, Takehiko Kamijo
    • Organizer
      Advanced Neuroblastoma Research 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications2018

    • Author(s)
      Zhenghao Li, Hisanori Takenobu, Amallia Nuggetsiana Setyawati, Nobuhiro Akita, Masayuki Haruta, Shunpei Satoh, Yoshitaka Shinno, Koji Chikaraishi, Kyosuke Mukae, Jesmin Akter, Ryuichi P. Sugino, Atsuko Nakazawa, Akira Nakagawara, Hiroyuki Aburatani, Miki Ohira, Takehiko Kamijo
    • Organizer
      Advanced Neuroblastoma Research 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CFC1 is a cancer stemness-regulating factor in neuroblastoma.2018

    • Author(s)
      Chikaraishi K, Takenobu H, Sugino RP, Mukae K, Akter J, Haruta M, Kurosumi M, Endo TA, Koseki H, Shimojo N, Ohira M, Kamijo T
    • Organizer
      Advanced Neuroblastoma Research 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of molecules that regulate the sensitivity of EZH2 inhibitor in neuroblastoma2018

    • Author(s)
      Yuki Endo, Hisanori Takenobu, Ryuichi Sugino, Masayuki Haruta, Kyosuke Mukae, Shunpei Satoh, Yoshitaka Shinno, Mariko Hasegawa, Ryu Okada, Yutaka Katai, Masaki Nio, Miki Ohira, Takehiko Kamijo
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Polycomb molecule L3MBTL2 suppresses apoptotic cell death cooperating with BMI1 in neuroblastoma2018

    • Author(s)
      Ryu Okada, Hisanori Takenobu, Miki Ohira, Ryuichi Sugino, Koji Chikaraishi, Nobuhiro Akita, Masayuki Haruta, Kyosuke Mukae, Yuki Endo, Shunpei Satoh, Yutaka Katai, Haruhiko Koseki, Takehiko Kamijo
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CDX1 regulates stemness through MYC pathway modulation and reprogramming gene activation in neuroblastoma2018

    • Author(s)
      Hisanori Takenobu, Miki Ohira, Ryuichi Sugino, Koji Chikaraishi, Ryu Okada, Kyosuke Mukae, Yuki Endo, Parvin Sultana, Yutaka Katai, Nobuhiro Akita, Masayuki Haruta, Haruhiko Koseki, Takehiko Kamijo
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of neuroblastoma model from iPS-based neural crest cells for analysis of neuroblastoma tumorigenesis2018

    • Author(s)
      Kyosuke Mukae, Hisanori Takenobu, Ryuichi Sugino, Miki Ohira, Shunpei Satoh, Yuki Endo, Ryu Okada, Masayuki Haruta, Junya Toguchida, Kenji Osafune, Tatsutoshi Nakahata, Takehiko Kamijo
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications2018

    • Author(s)
      Zhenghao Li, Hisanori Takenobu, Amallia Nuggetsiana Setyawati, Nobuhiro Akita, Masayuki Haruta, Shunpei Satoh, Yoshitaka Shinno, Koji Chikaraishi, Kyosuke Mukae, Jesmin Akter, Ryuichi P. Sugino, Atsuko Nakazawa, Akira Nakagawara, Hiroyuki Aburatani, Miki Ohira, Takehiko Kamijo
    • Organizer
      第60回 日本小児血液がん学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Screening of EZH2i effector molecules in neuroblastoma by multi-omics analysis2018

    • Author(s)
      Yuki Endo, Hisanori Takenobu, Ryuichi Sugino, Masayuki Haruta, Kyosuke Mukae, Shunpei Satoh, Yoshitaka Shinno, Mariko Hasegawa, Ryu Okada, Yutaka Katai, Masaki Nio, Miki Ohira, Takehiko Kamijo
    • Organizer
      第60回 日本小児血液がん学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effect of ATRX deletion by CRISPR-Cas9 system in neuroblastoma2018

    • Author(s)
      Yutaka Katai, Jesmin Akter, Hisanori Takenobu, Miki Ohira, Ryuichi Sugino, Masayuki Haruta, Shunpei Satoh, Kyosuke Mukae, Parvin Sultana, Takehiko Kamijo
    • Organizer
      第41回 日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Neuroblastoma cell dedifferentiation via epigenetic modification2018

    • Author(s)
      Hisanori Takenobu, Ryuichi P. Sugino, Miki Ohira, Takehiko Kamijo
    • Organizer
      第41回 日本分子生物学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] CFC1 regulates cancer stemness phenotypes in neuroblastoma via Activin signaling suppression2017

    • Author(s)
      Koji Chikaraishi, Hisanori Takenobu, Ryuichi Sugino, Kyosuke Mukae, Masayuki Haruta, Masafumi Kurosumi, Yoshitaka Shinno, Akter Jesmin, A Takaho Endo, Haruhiko Koseki, Miki Ohira, Takehiko Kamijo
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Sphere specific transcription factor CDX1 has dual functions for regulating stemness of neuroblastoma2017

    • Author(s)
      Hisanori Takenobu, Ryuichi Sugino, Miki Ohira, Koji Chikaraishi, Kyosuke Mukae, Masayuki Haruta, Haruhiko Koseki, Takehiko Kamijo
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Characterization of cell type by DNA methylation pattern using principal component analysis-based approach2017

    • Author(s)
      Ryuichi Sugino, Miki Ohira, Satoshi Yamashita, Hisanori Takenobu, Junya Toguchida, Toshikazu Ushijima, Takehiko Kamijo
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications2017

    • Author(s)
      Zhenghao Li, Hisanori Takenobu, Masayuki Haruta, Shunpei Satoh, Yoshitaka Shinno, Kyosuke Mukae, Jesmin Akter, Ryuichi Sugino, Akira Nakagawara, Hiroyuki Aburatani, Miki Ohira, Takehiko Kamijo
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] CRISPR/Cas9-based knockout of the chromatin remodeling factor ATRX and its effect in neuroblastoma (NB) cells2017

    • Author(s)
      Jesmin Akter, Yutaka Katai, Hisanori Takenobu, Masayuki Haruta, Parvin Sultana, Kyosuke Mukae, Ryuichi Sugino, Miki Ohira, Takehiko Kamijo
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications2017

    • Author(s)
      Hisanori Takenobu, Zhenghao Li, Masayuki Haruta, Shunpei Satoh, Yoshitaka Shinno, Kyosuke Mukae, Jesmin Akter, Ryuichi Sugino, Akira Nakagawara, Hiroyuki Aburatani, Miki Ohira, Takehiko Kamijo
    • Organizer
      The 3rd Asia-Pacific International Symposium of Neuroblastoma
    • Related Report
      2017 Research-status Report
  • [Presentation] EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications2017

    • Author(s)
      Hisanori Takenobu, Zhenghao Li, Amallia Nuggetsiana Setyawati, Nobuhiro Akita, Masayuki Haruta, Shunpei Satoh, Yoshitaka Shinno, Koji Chikaraishi, Kyosuke Mukae, Jesmin Akter, Yuki Endo, Ryuichi P. Sugino, Akira Nakagawara, Hiroyuki Aburatani, Miki Ohira, Takehiko Kamijo
    • Organizer
      第59回 日本小児血液がん学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Sphere specific transcription factor CDX1 regulates stemness of neuroblastoma2017

    • Author(s)
      Hisanori Takenobu, Ryuichi Sugino, Miki Ohira, Koji Chikaraishi, Kyosuke Mukae, Yuki Endo, Sultana Parvin, Ryu Okada, Yutaka Katai, Masayuki Haruta, Haruhiko Koseki, Takehiko Kamijo
    • Organizer
      第59回 日本小児血液がん学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Effect of CFC1 on cancer cell stemness in neuroblastoma2017

    • Author(s)
      Koji Chikaraishi, Hisanori Takenobu, Ryuichi Sugino, Kyosuke Mukae, Jesmin Akter, Masayuki Haruta, Masafumi Kurosumi, Takaho Endo, Haruhiko Koseki, Naoki Shimojo, Miki Ohira, Takehiko Kamijo
    • Organizer
      第59回 日本小児血液がん学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPS細胞を用いた神経芽腫発がんモデル2016

    • Author(s)
      Takenobu H, Sugino R, Ohira M, Yamashita S, Toguchida J, Kamijo T
    • Organizer
      第58回日本小児血液がん学会学術集会
    • Place of Presentation
      品川
    • Year and Date
      2016-12-15
    • Related Report
      2016 Research-status Report
  • [Presentation] CFC-1遺伝子は神経芽腫細胞の幹細胞化制御因子である2016

    • Author(s)
      Chikaraishi K, Takenobu H, Mukae K, Sugino R, Ohira M, Koseki H, Kamijo T
    • Organizer
      第58回日本小児血液がん学会学術集会
    • Place of Presentation
      品川
    • Year and Date
      2016-12-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 神経芽腫幹細胞を制御する新規シグナル経路の解析2016

    • Author(s)
      Hisanori Takenobu, Miki Ohira, Koji Chikaraishi, Kyosuke Mukae, Nobuhiro Akita, Masayuki Haruta, Haruhiko Koseki, Takehiko Kamijo
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] iPS細胞から神経堤細胞への分化における統合解析2016

    • Author(s)
      Sugino R, Ohira M, Yamashita S, Takenobu H, Toguchida J, Ushijima T, Kamijo T
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] EZH2による神経芽腫の分化抑制2016

    • Author(s)
      Li Z, Setyawati AN, Takenobu H, Akita N, Haruta M, Chikaraishi K, Mukae K, Akter J, Sugino R, Ohira M, Kamijo K
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] CDX1 regulates cancer stemness pathway in neuroblastoma, CDX1 regulates cancer stemness pathway in neuroblastoma2016

    • Author(s)
      Hisanori Takenobu, Miki Ohira, Koji Chikaraishi, Nobuhiro Akita, Yohko Yamaguchi, Masayuki Haruta, Akira Nakagawara, Manabu Nakayama, Haruhiko Koseki, Takehiko Kamijo
    • Organizer
      国際神経芽腫学会 (ANR2016)
    • Place of Presentation
      ケアンズ (オーストラリア)
    • Year and Date
      2016-06-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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