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2011 Fiscal Year Final Research Report

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

Research Project

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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
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
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.

  • Research Products

    (14 results)

All 2011 2010 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (7 results) Book (1 results) Remarks (1 results)

  • [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

    • 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

    • 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

    • 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

    • 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

    • Peer Reviewed
  • [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
    • Year and Date
      20111003-05
  • [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
    • Year and Date
      20110214-15
  • [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
  • [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
  • [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
    • Year and Date
      20101207-10
  • [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
    • Year and Date
      20101207-10
  • [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
    • Year and Date
      20100706-08
  • [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
  • [Remarks]

    • URL

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

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Published: 2013-07-31   Modified: 2014-12-04  

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