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Elucidation of Warburg effect in cancer with the next-generation proteomics

Research Project

Project/Area Number 26640080
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionKyushu University

Principal Investigator

NAKAYAMA Keiichi  九州大学, 生体防御医学研究所, 教授 (80291508)

Project Period (FY) 2014-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordsがん / プロテオミクス / ワールブルグ効果 / 代謝
Outline of Final Research Achievements

we developed a new platform (information-based MRM: iMRM) that allows genome-wide absolute quantification of the human proteome and is reliant on the production of ~18,000 recombinant proteins. We applied iMRM to delineate the metabolic landscape of human diploid fibroblasts. Oncogenic transformation of these cells gave rise to relatively small but global changes in metabolic pathways that account for aerobic glycolysis (Warburg effect) and increased rates of macromolecule synthesis. Modulation of metabolic enzyme expression revealed an unexpected functional interaction between glycolysis and the pentose phosphate pathway that facilitates nucleic acid synthesis. Furthermore, integration of proteomic and metabolomic data allowed construction of a mathematical model for identification of key enzymes responsible for the metabolic shift in cancer. Our results thus provide a global view of metabolic restructuring in cancer that underlies adaptation to a rapid growth state.

Report

(2 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (10 results)

All 2015 2014 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (5 results) (of which Invited: 5 results) Remarks (2 results)

  • [Journal Article] Reconstruction of insulin signal flow from phosphoproteome and metabolome data2014

    • Author(s)
      Yugi, K., Kubota, H., Toyoshima, Y., Noguchi, R., Kawata, K., Komori, Y., Uda, S., Kunida, K., Tomizawa, Y., Funato, Y., Miki, H., Matsumoto, M., Nakayama, K.I., Kashikura, K., Endo, K., Ikeda, K., Soga, T., Kuroda, S.
    • Journal Title

      Cell Rep.

      Volume: 8 Issue: 4 Pages: 1171-1183

    • DOI

      10.1016/j.celrep.2014.07.021

    • NAID

      120005537752

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX242014

    • Author(s)
      Yamauchi, T., Nishiyama, M., Moroishi, T., Yumimoto, K., Nakayama, K. I.
    • Journal Title

      Molecular and Cellular Biology

      Volume: 34 Issue: 17 Pages: 3321-3340

    • DOI

      10.1128/mcb.00320-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ZFP36L1 and ZFP36L2 control LDLR mRNA stability via the ERK-RSK pathway2014

    • Author(s)
      Adachi S, Homoto M, Tanaka R, Hioki Y, Murakami H, Suga H, Matsumoto M, Nakayama KI, Hatta T, Iemura S, Natsume T.
    • Journal Title

      Nucleic Acids Research

      Volume: 42 Issue: 15 Pages: 10037-10049

    • DOI

      10.1093/nar/gku652

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 次世代プロテオミクスを用いたがん特性の解明2015

    • Author(s)
      中山敬一
    • Organizer
      第45回ヒューマンサイエンス総合研究セミナー「がんの多様性に応じた研究・治療 ー 創薬のパラダイムシフト ー
    • Place of Presentation
      東京
    • Year and Date
      2015-01-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Deep and absolute quantification of human proteome unveils a global landscape of cancer metabolism2014

    • Author(s)
      Nakayama, K. I.
    • Organizer
      The 4th Japan-France Cancer Workshop
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2014-11-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 次世代プロテオミクスと数理科学の融合が解き明かすがんの秘密2014

    • Author(s)
      中山敬一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 全タンパク質の絶対定量によるがん代謝シフトの解明2014

    • Author(s)
      中山敬一
    • Organizer
      第14回日本蛋白質科学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-06-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 次世代プロテオミクスと数理科学の融合が解き明かすがんの秘密2014

    • Author(s)
      中山敬一
    • Organizer
      生命科学系3分野がん・ゲノム・脳支援活動合同シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 九州大学生体防御医学研究所分子医科学分野

    • URL

      http://www.bioreg.kyushu-u.ac.jp/saibou/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] Department of Molecular and Cellular Biology

    • URL

      http://www.bioreg.kyushu-u.ac.jp/saibou/index_en.html

    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2016-06-03  

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