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Identification of a protein phosphatase which involved in brain tumororigenesis.

Research Project

Project/Area Number 16K10774
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionMiyagi Prefectural Hospital Organization Miyagi Cancer Center

Principal Investigator

Yamashita Yoji  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (30420045)

Co-Investigator(Kenkyū-buntansha) 島 礼  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 部長 (10196462)
佐藤 郁郎  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), ティッシュバンクセンター, 部長 (50225918)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsプロテインホスファターゼ / 悪性グリオーマ / プロテインホスファターゼ6型 / glioma / CDC25A / 脳腫瘍学
Outline of Final Research Achievements

Ptprz/Protein tyrosine phosphatase receptor type Z is preferentially in neuronal and glial cells in the central nervous system as a major chondroitin sulfate proteoglycan, but its role in gliomagenesis remains obscure. In this study, expression of Ptprz mRNA was up-regulated in glioma when compared to normal brain. We found that the levels of Ptprz mRNA in specimens are correlated with those of Sox-2, a transcription factor associating with glioma stemness. Knock-down of Sox-2 by siRNA decreased Ptprz mRNA of several glioma cell lines. ChIP analysis showed the physical association of Sox-2 to the putative promoter region of Ptprz gene, suggesting that Ptprz is a direct transcriptional target of Sox-2. Up-regulation of Ptprz expression may be a part of transcriptional program elicited by Sox-2, which may contribute to glioma stemness.

Academic Significance and Societal Importance of the Research Achievements

がんの発生原因として幾つかのプロテインキナーゼがその原因となっていることが明らかとなってきた。一方で、拮抗する機能をもつホスファターゼに関しては研究が遅れていた。
本研究により我々は、悪性グリオーマの治療開発のための新たな分子標的を同定する目的で、プロテインホスファターゼ遺伝子の発現異常の有無をスクリーニングし、発現量が顕著に上昇してい分子の一つとしてPTPzetaを同定した。悪性グリオーマの新しい診断・治療法の開発が期待できる。

Report

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

    (11 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (6 results)

  • [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes enhances K-ras G12D -driven tumor promotion2018

    • Author(s)
      Kurosawa Koreyuki、Inoue Yui、Kakugawa Yoichiro、Yamashita Yoji、Kanazawa Kosuke、Kishimoto Kazuhiro、Nomura Miyuki、Momoi Yuki、Sato Ikuro、Chiba Natsuko、Suzuki Mai、Ogoh Honami、Yamada Hidekazu、Miura Koh、Watanabe Toshio、Tanuma Nobuhiro、Tachi Masahiro、Shima Hiroshi
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 7 Pages: 2178-2187

    • DOI

      10.1111/cas.13638

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Indications for salvage surgery during treatment for intracranial germ cell tumors.2018

    • Author(s)
      Kanamori M, Kumabe T, Watanabe M, Chonan M, Saito R, Yamashita Y, Ogawa Y, Sonoda Y, Tominaga T.
    • Journal Title

      J Neurooncol.

      Volume: - Issue: 3 Pages: 601-607

    • DOI

      10.1007/s11060-018-2827-3

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth.2018

    • Author(s)
      M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
    • Journal Title

      Cancer Cell

      Volume: 12 Issue: 3 Pages: 355-367

    • DOI

      10.1016/j.ccell.2018.02.004

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes enhances K-rasG12D-driven tumor promotion.2018

    • Author(s)
      Kurosawa K, Inoue Y, Kakugawa Y, Yamashita Y, Kanazawa K, Kishimoto K, Nomura M, Momoi Y, Sato I, Chiba N, Suzuki M, Ogoh H, Yamada H, Miura K, Watanabe T, Tanuma N, Tachi M, and Shima H
    • Journal Title

      Cancer Science

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sialidase NEU3 defines invasive potential of human glioblastoma cells by regulating calpain-mediated proteolysis of focal adhesion proteins2017

    • Author(s)
      Takahashi Kohta、Proshin Sergei、Yamaguchi Kazunori、Yamashita Yoji、Katakura Ryuichi、Yamamoto Koji、Shima Hiroshi、Hosono Masahiro、Miyagi Taeko
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1861 Issue: 11 Pages: 2778-2788

    • DOI

      10.1016/j.bbagen.2017.07.023

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Ppp6c は、マウス皮膚のがん抑制遺伝子として働く2017

    • Author(s)
      黒沢是之、野村美有樹、角川陽一郎、山下洋二、三浦康、山田秀和、松浦一登、佐藤郁郎、田沼延公、渡邊利雄、島礼
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規皮膚がん抑制遺伝子Ppp6c変異は、変異型K-RASによる腫瘍発生を強く促進する2016

    • Author(s)
      黒沢是之、田沼延公、角川陽一郎、山下洋二、三浦康、山田秀和、佐藤郁郎、野村美有樹、渡利雄、島礼
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      神奈川県・横浜市
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] PKMノックアウトマウスは胎生致死となる2016

    • Author(s)
      田中遼太、渡邊利雄、山下洋二、三浦康、佐藤郁郎、島礼、田沼延公
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      神奈川県・横浜市
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Pyruvate kinase Mの両isoformを欠損するマウスの解析2016

    • Author(s)
      田中遼太、小河穂波、井上維、山下洋二、三浦康、河合賢郎、佐藤郁郎、渡邊利雄、島礼、田沼延公
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      宮城県・仙台市
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 80歳を超える高齢悪性神経膠腫患者の治療2016

    • Author(s)
      山下洋二、冨永悌二、片倉隆一
    • Organizer
      日本脳神経外科学会 第75回学術総会
    • Place of Presentation
      福岡県・福岡市
    • Related Report
      2016 Research-status Report
  • [Presentation] 75歳を超える高齢悪性神経膠腫患者の治療2016

    • Author(s)
      山下洋二、冨永悌二、片倉隆一
    • Organizer
      第34回日本脳腫瘍学会学術集会
    • Place of Presentation
      山梨県・甲府市
    • Related Report
      2016 Research-status Report

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

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