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Next-generation proteomics to reveal the mechanism for malignant transformation

Research Project

Project/Area Number 17K19606
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Tumor biology and related fields
Research InstitutionKyushu University

Principal Investigator

Masaki Matsumoto  九州大学, 生体防御医学研究所, 准教授 (60380531)

Research Collaborator Nakayama Keiichi  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsプロテオミクス / 代謝 / がん / がん代謝 / プロテオーム / 癌
Outline of Final Research Achievements

In this study, we established an in vitro model for malignant transformation from oncogene-induced pre-cancerous state cell line. In order to reveal the molecular basis of malignant transformation, the expression level of metabolic enzymes in these cell lines was quantified by our originally developed next-generation proteomics, iMPAQT. We found that glutamine metabolism is significantly altered during malignant transformation and PPAT which transfers nitrogen to 5-phosphoribosyl-1-pyrophosphate (PRPP), a precursor in nucleotide biosynthesis, from glutamine, acts as a key enzyme in cancer specific glutamine metabolism. We also demonstrated that attenuation of PPAT induces the reduction in the tumor size.

Academic Significance and Societal Importance of the Research Achievements

本研究によってがんの悪性進展過程においてグルタミン代謝経路が核酸合成に偏重してシフトしていることを見出した。このがん特有の代謝シフトの原因であるPPATの発現抑制によって腫瘍形成を減弱させることができたことから、この酵素が抗がん剤の有効なターゲットとなり得ることが示唆された。また、代謝酵素の一斉定量法を確立したことで、広範な疾患の分子機構を代謝経路の変化として捉えることが可能となった。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report

Research Products

(13 results)

All 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] The jPOST environment: an integrated proteomics data repository and database2019

    • Author(s)
      Moriya Yuki、Kawano Shin、Okuda Shujiro、Watanabe Yu、Matsumoto Masaki、Takami Tomoyo、Kobayashi Daiki、Yamanouchi Yoshinori、Araki Norie、Yoshizawa Akiyasu C、Tabata Tsuyoshi、Iwasaki Mio、Sugiyama Naoyuki、Tanaka Satoshi、Goto Susumu、Ishihama Yasushi
    • Journal Title

      Nucl Acids Res

      Volume: 47 Pages: 1218-1224

    • DOI

      10.1093/nar/gky899

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb162018

    • Author(s)
      Hosokawa Hiroyuki、Romero-Wolf Maile、Yui Mary A.、Ungerb?ck Jonas、Quiloan Maria L. G.、Matsumoto Masaki、Nakayama Keiichi I.、Tanaka Tomoaki、Rothenberg Ellen V.
    • Journal Title

      Nature Immunology

      Volume: 19 Pages: 1427-1440

    • DOI

      10.1038/s41590-018-0238-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of the physiological substrates of PDIp, a pancreas-specific protein-disulfide isomerase family member2018

    • Author(s)
      Fujimoto Takushi、Nakamura Orie、Saito Michiko、Tsuru Akio、Matsumoto Masaki、Kohno Kenji、Inaba Kenji、Kadokura Hiroshi
    • Journal Title

      J Biol Chem

      Volume: 293 Pages: 18421-18433

    • DOI

      10.1074/jbc.ra118.003694

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks2018

    • Author(s)
      Kawata Kentaro、Hatano Atsushi、Yugi Katsuyuki、Kubota Hiroyuki、Sano Takanori、Fujii Masashi、Tomizawa Yoko、Kokaji Toshiya、Tanaka Kaori Y.、Uda Shinsuke、Suzuki Yutaka、Matsumoto Masaki、Nakayama Keiichi I.、Saitoh Kaori、Kato Keiko、Ueno Ayano、Ohishi Maki、Hirayama Akiyoshi、Soga Tomoyoshi、Kuroda Shinya
    • Journal Title

      iScience

      Volume: 7 Pages: 212-229

    • DOI

      10.1016/j.isci.2018.07.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding2018

    • Author(s)
      Hosokawa Hiroyuki、Ungerb?ck Jonas、Wang Xun、Matsumoto Masaki、Nakayama Keiichi I.、Cohen Sarah M.、Tanaka Tomoaki、Rothenberg Ellen V.
    • Journal Title

      Immunity

      Volume: 48

    • DOI

      10.1016/j.immuni.2018.04.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 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] The promise of targeted proteomics for quantitative network biology2018

    • Author(s)
      Matsumoto Masaki、Nakayama Keiichi I
    • Journal Title

      Curr Opin Biotechnol.

      Volume: 54 Pages: 88-97

    • DOI

      10.1016/j.copbio.2018.02.014

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages2017

    • Author(s)
      Nakatsumi Hirokazu、Matsumoto Masaki、Nakayama Keiichi I.
    • Journal Title

      Cell Rep.

      Volume: 21 Pages: 2471-2486

    • DOI

      10.1016/j.celrep.2017.11.014

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] iMPAQT: a scalable and flexible platform for the quantification of proteins of interest2018

    • Author(s)
      松本 雅記、中山 敬一
    • Organizer
      第91回日本生化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] iMPAQT ver.2.0: 拡張性と柔軟性を備えたタンパク質絶対定量プラットフォーム2018

    • Author(s)
      松本 雅記、中山 敬一
    • Organizer
      MSP2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] Robotics promotes accurate and reproducible data acquisition in proteomics2018

    • Author(s)
      Masaki Matsumoto
    • Organizer
      Robotics and Semantic Systems for Biology Symposium 2
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] iMPAQT: A Platform for Large-Scale Targeted Proteomics Based on an in Vitro Human Proteome2017

    • Author(s)
      松本雅記、中山敬一
    • Organizer
      JPrOS2017年大会
    • Related Report
      2017 Research-status Report
  • [Presentation] iMPAQT: A platform for large-scale targeted proteomics based on an in vitro human proteome2017

    • Author(s)
      松本雅記
    • Organizer
      第65質量分析総合討論会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-07-21   Modified: 2020-03-30  

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