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Cancer metabolic reprogramming in human pancreatic cancer cells under nutrient-deprived conditions

Research Project

Project/Area Number 17K15000
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionMicrobial Chemistry Research Foundation

Principal Investigator

Onodera Takefumi  公益財団法人微生物化学研究会, 微生物化学研究所 沼津支所, 研究員 (20733166)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsがん代謝 / 低栄養 / ペントースリン産経路 / 膵がん / ペントースリン酸経路 / 栄養飢餓 / ペントースリン酸回路
Outline of Final Research Achievements

Cancer tissues maintain growth and survival by metabolic reprogramming to adapt tumor microenvironments such as hypoxia and nutrient-deprived conditions. Targeting cancer-specific metabolism to molecular-targeted therapeutics holds promise as a novel anticancer strategy. In the present study, we found that the expression level of transketolase family genes that function in the pentose phosphate pathway greatly increased under nutrient-deprived conditions. Therefore, we investigated the role of these genes and evaluated the potential for candidate gene in cancer treatment. As a result, overexpression of transketolase family genes promoted cell proliferation, and knockdown of the genes reduced cell proliferation. These findings suggest that transketolase family genes may be attractive targets for anticancer drug therapy.

Academic Significance and Societal Importance of the Research Achievements

がん微小腫瘍環境を一つである栄養欠乏状態を模倣した環境において、ペントースリン酸経路内のトランスケトラーゼ関連遺伝子が高発現していることを見出し、がんにおけるトランスケトラーゼ関連遺伝子の機能解明を行った。これまで、トランスケトラーゼ関連遺伝子の機能についての詳細はよく分かっていなかったが、in vitroおよびin vivo実験結果から、トランスケトラーゼ関連遺伝子を抑制すれば、腫瘍増大を阻止できることが示唆された。本研究は、トランスケトラーゼ関連遺伝子産物の阻害剤の開発および、エネルギー代謝を標的とした新しいがん治療法の科学的基盤になることが期待される。

Report

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

    (8 results)

All 2019 Other

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

  • [Journal Article] Potential Anticancer Activity of Auranofin2019

    • Author(s)
      T. Onodera, I. Momose, M. Kawada
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 67 Issue: 3 Pages: 186-191

    • DOI

      10.1248/cpb.c18-00767

    • NAID

      130007607281

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2019-03-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leucinostatin Y: A Peptaibiotic Produced by the Entomoparasitic Fungus Purpureocillium lilacinum 40-H-28.2019

    • Author(s)
      I. Momose, T. Onodera, H. Doi, H. Adachi, M. Iijima, Y. Yamazaki, R. Sawa, Y. Kubota, M. Igarashi, M. Kawada
    • Journal Title

      J. Nat. Prod.

      Volume: 印刷中 Issue: 5 Pages: 1120-1127

    • DOI

      10.1021/acs.jnatprod.8b00839

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 低栄養環境におけるがん特異的代謝リプログラミング機構の解明2019

    • Author(s)
      百瀬功、小野寺威文、坂本修一、川田学
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] レドックス制御システムの阻害による栄養欠乏選択的細胞毒性2019

    • Author(s)
      百瀬功、小野寺威文、山崎洋子、大庭俊一、安達勇光、川田学
    • Organizer
      第23回日本がん分子標的治療学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Takefumi Onodera, shun-ich Ohba, Isao Momose, Manabu Kawada2019

    • Author(s)
      Inhibitory effect of a redox system by auranofin in pancreatic cancer cells under nutrient-deprived conditions.
    • Organizer
      11th AACR-JCA Joint Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 公益財団法人微生物化学研究会 微生物化学研究所 HP

    • URL

      https://www.bikaken.or.jp

    • Related Report
      2019 Annual Research Report
  • [Remarks] (公財)微生物化学研究会 微生物化学研究所

    • URL

      http://www.bikaken.or.jp

    • Related Report
      2018 Research-status Report
  • [Remarks] 微化研ホームページ

    • URL

      http://www.bikaken.or.jp

    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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