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Functional role of PPP3CB in neuroblastoma and potential anti-tumor effect of calcineurin inhibitor on neuroblastoma

Research Project

Project/Area Number 15K10933
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research Institution地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所)

Principal Investigator

LI YUANYUAN  地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所), ライフサイエンス研究所, 研究員 (00392259)

Co-Investigator(Kenkyū-buntansha) 中川原 章  地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所), ライフサイエンス研究所, 理事長 (50117181)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords神経芽腫 / PPP3CB / calcineurin inhibitor / PPP3CB
Outline of Final Research Achievements

PPP3CB is the catalytic subunit of calcineurin, a calcium-dependent serine/threonine phosphatase. In this study we found that overexpression of wildtype PPP3CB or constitutively active PPP3CB mutant (PPP3CBmut) identified from a neuroblastoma (NB) tumor promoted cell growth in NB cells. PPP3CB and PPP3CBmut activated nuclear factor of activated T-cells (NFAT)2 /NFAT4 transcription factors, Akt and MAPK signaling, resulting in the increase in the expressions of c-Myc, MYCN and β-catenin. Treatment with calcineurin inhibitors (CaIs) suppressed cell proliferation and induced apoptotic cell death in several NB cell lines. Expression of PPP3CB along with those of c-Myc, MYCN and β-catenin was decreased in response to CaIs. Our findings demonstrate that PPP3CB contributes to the aggressive behavior of NB tumors and CaIs have a strong anti-tumor activity in vitro by targeting PPP3CB, suggesting that inhibition of calcineurin activity might have therapeutic potential for high-risk NBs.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Neuroblastoma2018

    • Author(s)
      Nakagawara Akira、Li Yuanyuan、Izumi Hideki、Muramori Katsumi、Inada Hiroko、Nishi Masanori
    • Journal Title

      Jpn. J. Clin. Oncol.

      Volume: 48 Issue: 3 Pages: 214-241

    • DOI

      10.1093/jjco/hyx176

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic analysis–integrated whole-exome sequencing of neuroblastomas identifies genetic mutations in axon guidance pathway2017

    • Author(s)
      Li Yuanyuan、Ohira Miki、Zhou Yong、Xiong Teng、Luo Wen、Yang Chao、Li Xiangchun、Gao Zhibo、Zhou Rui、Nakamura Yohko、Kamijo Takehiko、Kaneko Yasuhiko、Taketani Takeshi、Ueyama Junichi、Tajiri Tatsuro、Zhang Hongyan、Wang Jian、Yang Huanming、Yin Ye、Nakagawara Akira
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 34 Pages: 56684-56697

    • DOI

      10.18632/oncotarget.18079

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Familial neuroblastoma(家族性神経芽腫)2015

    • Author(s)
      李元元, 木下儀晶, 中川原章
    • Journal Title

      日本臨牀

      Volume: 73(1083) Pages: 108-114

    • Related Report
      2015 Research-status Report
  • [Presentation] Genomic Analysis-Integrated Whole-exome Sequencing of Neuroblastomas2017

    • Author(s)
      Li Y and Nakagawara A
    • Organizer
      The 3rd China International Forum of Pediatric Development
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] PPP3CB is a novel prognostic indicator of high-risk neuroblastoma contributing to aggressive behaviors.2016

    • Author(s)
      Yuanyuan Li, Irina Shakhova, Miki Ohira, Yohko Nakamura, Svetlana R. Varfolomeeva, Alexander G. Rumyantsev and Akira Nakagawara.
    • Organizer
      Advances in Neuroblastoma Research (ANR)
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      2016-06-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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