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Lipid metabolomics to analyze the mechanisms for cellular adaptation to tumor microenvironment

Research Project

Project/Area Number 22650230
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Tumor biology
Research Institution公益財団法人がん研究会 (2011)
Japanese Foundation For Cancer Research (2010)

Principal Investigator

SEIMIYA Hiroyuki  公益財団法人がん研究会, がん化学療法センター分子生物治療研究部, 部長 (50280623)

Co-Investigator(Kenkyū-buntansha) MIGITA Toshiro  がん研究会, がん化学療法センター分子生物治療研究部, 研究員 (20462236)
MASHIMA Tetsuo  がん研究会, がん化学療法センター分子生物治療研究部, 研究員 (30311228)
Co-Investigator(Renkei-kenkyūsha) TAGUCHI Ryo  中部大学, 大学院・生命健康科学研究科, 教授 (20080210)
SAITO Shinichi  東京理科大学, 理学部・第一化学科, 教授 (80283076)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,320,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords脂質代謝 / 細胞増殖 / がん / 微小環境 / メタボローム / ATP-クエン酸リアーゼ / 活性酸素 / 酸化ストレス / 脂質 / バイオマーカー / 細胞死
Research Abstract

Cancer cells often enhance de novo lipid synthesis. However, its functional significance remains unknown. In this study, we found that depletion of a lipid-synthesizing enzyme, called ATP citrate lyase(ACLY), blocks cancer cell growth. This anticancer effect was more evident in those cells with lower reactive oxygen species(ROS) and lower phosphorylation level of AMPK. ACLY depletion elevated the relative abundance of palmitate. Because palmitate can induce ROS, it may contribute to the anticancer effect of ACLY depletion. In clinical colon tumors, higher malignant grades correlated with lower levels of AMPK phosphorylation and oxidative stress, suggesting that ACLY inhibition can be utilized as an anticancer therapeutics.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (27 results)

All 2012 2011 2010 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (11 results) Book (1 results) Remarks (3 results)

  • [Journal Article] JBIR-120: a new growth inhibitor of hormone-refractory prostate cancer cells.2012

    • Author(s)
      Kawahara, T.
    • Journal Title

      J Antibiot

      Volume: 65 Issue: 7 Pages: 373-375

    • DOI

      10.1038/ja.2012.32

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of acyl-CoA synthetases in glioma cell survival and its therapeutic implication2011

    • Author(s)
      Mashima, T., Seimiya, H.
    • Journal Title

      Tumors of the Central Nervous System

      Volume: 1 Pages: 337-340

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular pharmacological approach reveals potential new strategies to suppress androgen receptor signaling in prostate cancer2011

    • Author(s)
      Mashima, T., Okabe, S., Seimiya, H.
    • Journal Title

      Mol Cell Pharmacol

      Volume: 3 Pages: 7-12

    • Related Report
      2011 Annual Research Report 2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fission yeast potl and recQ helicase are required for efficient chromosome segregation2011

    • Author(s)
      Takahashi, K.
    • Journal Title

      Mol Cell Biol

      Volume: 31 Pages: 495-506

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacological targeting of constitutively active truncated androgen receptor by nigericin and suppression of hormone-refractory prostate cancer cell growth2010

    • Author(s)
      Mashima, T., Okabe, S., Seimiya, H.
    • Journal Title

      Mol Pharmacol

      Volume: 78 Pages: 846-854

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of insulin-like growth factor binding protein 2 in lung adenocarcinoma : IGF-independent antiapoptotic effect via caspase-32010

    • Author(s)
      Migita, T., Narita, T., Asaka, R., Miyagi, E., Nagano, H., Nomura, K., Matsuura, M., Satoh, Y., Okumura, S., Nakagawa, K., Seimiya, H., Ishikawa, Y.
    • Journal Title

      Am J Pathol

      Volume: 176 Pages: 1756-1766

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRF1 mediates mitotic abnormalities induced by Aurora-A overexpression2010

    • Author(s)
      Ohishi, T., Hirota, T., Tsuruo, T., Seimiya, H.
    • Journal Title

      Cancer Res

      Volume: 70 Pages: 2041-2052

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tankyrase-1 assembly to large protein complexes blocks its telomeric function2010

    • Author(s)
      Hatsugai, K.
    • Journal Title

      FEBS Lett

      Volume: 584 Pages: 3885-3890

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of mutant RPA in human cancer cells causes telomere shortening2010

    • Author(s)
      Kobayashi, Y.
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 74 Pages: 382-385

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells2010

    • Author(s)
      Seki, T.
    • Journal Title

      Cell Stem Cell

      Volume: 7 Pages: 11-14

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualization of G-quadruplexes by using a BODIPY-labeled macrocyclic heptaoxazole2010

    • Author(s)
      Tera, M.
    • Journal Title

      Org Biomol Chem

      Volume: 8 Pages: 2749-2755

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor2010

    • Author(s)
      Yashiroda, Y.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 394 Pages: 569-573

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Inhibition of ATP citrate lyase mediates anticancer effects via reactive oxygen species and triglyceride accumulation2011

    • Author(s)
      右田敏郎
    • Organizer
      第15回日本癌学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県)(招待講演)
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] がんとは何でしょう?2011

    • Author(s)
      清宮啓之
    • Organizer
      新学術領域研究「がん研究分野の特性等を踏まえた支援活動」青少年・市民公開講座~いま知っておきたい「がん」のこと~
    • Place of Presentation
      福島県立医科大学(福島県)(招待講演)
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] 脂質代謝酵素を標的とした乳癌、前立腺癌の治療とその分子機構2011

    • Author(s)
      右田敏郎、岡部幸子、清宮啓之
    • Organizer
      第11回関東ホルモンと癌研究会
    • Place of Presentation
      東京
    • Year and Date
      2011-01-29
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] ナイジェリシンによる恒常活性化型アンドロゲン受容体の抑制はホルモン再燃性前立腺がん細胞増殖を阻害する2011

    • Author(s)
      馬島哲夫、岡部幸子、清宮啓之
    • Organizer
      第11回関東ホルモンと癌研究会
    • Place of Presentation
      東京
    • Year and Date
      2011-01-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Inhibition of ATP citrate lyase mediates anticancer effects via reactive oxygen species and triglyceride accumulation2011

    • Author(s)
      右田敏郎、岡部幸子、池田和貴、曽我朋義、田口良、清宮啓之
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] Involvement of constitutively active truncated androgen receptor(tAR) in hormone-refractory prostate cancer growth and the tAR inhibition by nigericin2011

    • Author(s)
      Mashima T., Okabe S., Seimiya H.
    • Organizer
      第10回日韓がん老化合同シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] がん細胞の増殖・生存における脂質代謝酵素の役割2010

    • Author(s)
      岡部幸子
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] 脂質代謝酵素の阻害によるがん細胞死とその分子機構2010

    • Author(s)
      右田敏郎
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会・ワークショップ
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] 脂質代謝酵素の阻害によるがん細胞死とその分子機構2010

    • Author(s)
      右田敏郎、岡部幸子、清宮啓之
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会・ワークショップ
    • Place of Presentation
      神戸
    • Related Report
      2011 Final Research Report
  • [Presentation] がん細胞の増殖・生存における脂質代謝酵素の役割2010

    • Author(s)
      岡部幸子、右田敏郎、馬島哲夫、清宮啓之
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂質代謝酵素の阻害による制がん効果とその分子メカニズム2010

    • Author(s)
      右田敏郎、岡部幸子、清宮啓之
    • Organizer
      第14回日本がん分子標的治療学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Book] がんにおける脂質代謝、実験医学増刊号「がんと代謝」

    • Author(s)
      右田敏郎、馬島哲夫、清宮啓之
    • Publisher
      羊土社
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/molecular_biotherapy/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/molecular_biotherapy/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/molecular_biotherapy/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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