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Development of novel anti-cancer strategy targeting protein phosphatases

Research Project

Project/Area Number 17H03915
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Veterinary medical science
Research InstitutionYamaguchi University

Principal Investigator

Ohama Takashi  山口大学, 共同獣医学部, 准教授 (50579018)

Co-Investigator(Kenkyū-buntansha) 大松 勉  東京農工大学, 農学部, 准教授 (60455392)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywordsがん幹細胞 / PP2A / 骨肉腫 / 比較腫瘍学 / SET / E2F1 / がん / 薬理学
Outline of Final Research Achievements

This project aimed to propose the efficacy of anti-cancer drug development targeting protein phosphatase activation, by clearing the role of SET/I2PP2A, an endogenous inhibitory protein for protein phosphatase 2A (PP2A), on cancer promotion. We revealed the molecular mechanisms of SET-mediating cancer promotion in canine mammary tumors, canine osteosarcomas, and human various tumors including stomach cancers. We also found that SET-targeting drugs exert anti-cancer effects on these canine and human cancers. We published five original papers for these research findings, and are preparing for the submission for two sub-projects.

Academic Significance and Societal Importance of the Research Achievements

本研究は、リン酸化酵素キナーゼに対する阻害剤に偏重している分子標的抗がん剤開発の分野に「ホスファターゼを活性化する」創薬という新たな視座を提供するための基盤的研究である。この視座に立った創薬は、従来の「キナーゼを阻害する」薬剤と相加・相乗効果が期待できるだけでなく、ホスファターゼ活性の低下はキナーゼ阻害剤に対する耐性の獲得にも重要であることから、キナーゼ阻害剤に抵抗性または耐性を獲得した症例に対しても効果が期待でき、ファースト・イン・クラスの画期的な創薬に繋がる可能性を秘めている。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (23 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (16 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results)

  • [Int'l Joint Research] National Chung Hsing University(Taiwan)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Distribution of SET/I2PP2A protein in gastrointestinal tissues.2019

    • Author(s)
      Umata K, Sakai Y, Ikeda S, Tsuji S, Kawasaki H, Ohama T, Sato K
    • Journal Title

      PloS One

      Volume: 14 Issue: 9 Pages: e0222845-e0222845

    • DOI

      10.1371/journal.pone.0222845

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of an anti-cancer strategy targeting SET in canine osteosarcoma2019

    • Author(s)
      TSUJI Shunya、OHAMA Takashi、NAKAGAWA Takayuki、SATO Koichi
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 81 Issue: 10 Pages: 1424-1430

    • DOI

      10.1292/jvms.19-0311

    • NAID

      130007730596

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The multiple functions of protein phosphatase 62019

    • Author(s)
      Ohama Takashi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1866 Issue: 1 Pages: 74-82

    • DOI

      10.1016/j.bbamcr.2018.07.015

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A stable association with PME-1 may be dispensable for PP2A demethylation - implications for the detection of PP2A methylation and immunoprecipitation -2018

    • Author(s)
      Yabe R, Tsuji S, Mochida S, Ikehara T, Usui T, Ohama T*, Sato K
    • Journal Title

      FEBS Open Bio

      Volume: 8(9) Pages: 1486-1496

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis2018

    • Author(s)
      Enjoji Shuhei、Yabe Ryotaro、Tsuji Shunya、Yoshimura Kazuhiro、Kawasaki Hideyoshi、Sakurai Masashi、Sakai Yusuke、Takenouchi Hiroko、Yoshino Shigefumi、Hazama Shoichi、Nagano Hiroaki、Oshima Hiroko、Oshima Masanobu、Vitek Michael P.、Matsuura Tetsuya、Hippo Yoshitaka、Usui Tatsuya、Ohama Takashi、Sato Koichi
    • Journal Title

      Molecular Cancer Research

      Volume: 16 Issue: 3 Pages: 554-563

    • DOI

      10.1158/1541-7786.mcr-17-0393

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The role of SET/I2PP2A in canine mammary tumors2017

    • Author(s)
      Kake Satoru、Tsuji Shunya、Enjoji Shuhei、Hanasaki Sayaka、Hayase Hiroshi、Yabe Ryotaro、Tanaka Yuiko、Nakagawa Takayuki、Liu Hao-Ping、Chang Shih-Chieh、Usui Tatsuya、Ohama Takashi、Sato Koichi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 4279-4279

    • DOI

      10.1038/s41598-017-04291-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Targeting PP2A inhibitory protein SET for cancer drug development2019

    • Author(s)
      Ohama T
    • Organizer
      4th TW-JP Bilateral Phosphatase Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Luciferase-based protein-protein interaction assay in living cells revealed SET dimerization to be essential for association with PP2A-B56 complex2019

    • Author(s)
      Tsuji S, Ikeda S, Shibutani S, Enjoji S, Ikeara S, Ohama T, Sato K
    • Organizer
      Europhosphatase2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Protein phosphatase 2Aとその阻害タンパク質PME-1のタンパク質間結合を制御する分子機構の解明2019

    • Author(s)
      松本真春、大山ゆき、大浜剛、佐藤晃一
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Protein phosphatase 2A阻害タンパク質SETの骨肉腫における役割2019

    • Author(s)
      幸柳尚規、辻竣也、大浜剛、佐藤晃一
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] PP2A阻害タンパク質SETによる癌悪性化機構2019

    • Author(s)
      大浜剛
    • Organizer
      第92回日本生化学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肺がん細胞A549においてPP2A複合体とその阻害タンパク質PME-1の果たす役割の解明2019

    • Author(s)
      池田俊太、大山ゆき、大浜剛、佐藤晃一
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Synergistic anti-cancer effects of PME-1 suppression and p53 activation on A549 cells2019

    • Author(s)
      Shunta Ikeda, Yuki Oyama, Tsuji Shunya, Takashi Ohama, Koichi Sato
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Presentation] The role of SET in Gastric Cancer2018

    • Author(s)
      Ohama T
    • Organizer
      Workshop on Frontiers in Phosphatase Research and Drug Discovery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] SET dimerization regulates PP2A/B56 association2018

    • Author(s)
      Tsuji S, Kake S, Enjoji S, Ohama T, Sato K
    • Organizer
      Workshop on Frontiers in Phosphatase Research and Drug Discovery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of SET dimerization restores activity of tumor suppressing phosphatase PP2A/B56α2018

    • Author(s)
      Shunya Tsuji, Shuhei Enjoji, Takashi Ohama, Koichi Sato
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Stemness is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis2018

    • Author(s)
      Takashi Ohama
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SETはPP2A活性阻害を介してE2F1を安定化することで、胃がんの幹細胞性の維持に関与する2018

    • Author(s)
      辻竣也、円城寺秀平、臼井達哉、大浜剛、佐藤晃一
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The role of SET/I2PP2A in canine mammary tumors2017

    • Author(s)
      Tsuji S, Kake S, Enjoji S, Ohama T, Sato K
    • Organizer
      Europhosphatase2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of Autophagy by Type2A Protein Phosphatases2017

    • Author(s)
      Ohama T, Fujiwara N, Sato K
    • Organizer
      Europhosphatase2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SET/I2PP2A Is a Prognostic Marker and a Potential Therapeutic Target for Gastric Cancer.2017

    • Author(s)
      Enjoji S, Ohama T, Sato K
    • Organizer
      Europhosphatase2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SET/I2PP2A Is a Prognostic Marker and a Potential Therapeutic Target for Gastric Cancer.2017

    • Author(s)
      大浜剛、円城寺秀平、佐藤晃一
    • Organizer
      第8回日本プロテインホスファターゼ研究会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-08-05  

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