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Stress response of cancer cells focusing the sphingolipid metabolism and its modulation by food ingredients

Research Project

Project/Area Number 26460674
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionChubu University (2015-2016)
Nagoya University (2014)

Principal Investigator

MURATE Takashi  中部大学, 生命健康科学部, 教授 (30239537)

Co-Investigator(Kenkyū-buntansha) 高木 明  名古屋大学, 医学系研究科(保健), 准教授 (30135371)
小嶋 哲人  名古屋大学, 医学系研究科(保健), 教授 (40161913)
鈴木 元  名古屋大学, 医学系研究科, 准教授 (80236017)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsSphingolipid metabolism / Cancer cell / Stress response / Food ingredient / Phytochemical / Anti-cancer action / レスベラトロール / 酸性スフィンゴミエリナーゼ / 転写調節 / 白血病細胞株 / 悪性腫瘍細胞株 / スフィンゴ脂質代謝 / 代謝酵素遺伝子発現調節 / SPHK2 / 血清除去 / ACDase / 前立腺癌細胞株 / アンドロジェン / USP2 / hypoxia / serum-depleted condition / CREB / transcription
Outline of Final Research Achievements

We have published 9 papers corresponding to the main title of the grant No. 26460674 between 2013 and 2016. Among them, 6 papers described the stress responses and the sphingolipid metabolism of cancer cells, whereas 2 papers analyzed the anti-cancer drug resistance of malignant cells. One paper elucidated the molecular mechanism of anti-cancer function of resveratrol, a food ingredient.
Based on these works, we concluded that malignant cells utilize heterogeneous mechanisms including aberrant sphingolipid metabolism, changes of DNA repair system, microtubules dynamics, mRNA half-life, and chromatin remodeling. As far as the sphingolipid metabolism was concerned, our data strongly supported the validity of the sphingolipid rheostat model telling that the balance between ceramide and sphingosine 1-phospahte determined cells' fate such as cell growth, survival, motion and differentiation.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2016 2015 2014

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results)

  • [Journal Article] Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells.2016

    • Author(s)
      Mizutani N, Omori Y, Kawamoto Y, Sobue S, Ichihara M, Suzuki M, Kyogashima M, Nakamura M, Tamiya-Koizumi K, Nozawa Y, Murate T.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 470 Issue: 4 Pages: 851-856

    • DOI

      10.1016/j.bbrc.2016.01.134

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of paclitaxel resistance in a human prostate cancer cell line, PC3-PR, and its sensitization by cabazitaxel2016

    • Author(s)
      Sobue S, Mizutani N, Aoyama Y, Kawamoto Y, Suzuki M, Nozawa Y, Ichihara M, Murate T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 479 Issue: 4 Pages: 808-813

    • DOI

      10.1016/j.bbrc.2016.09.128

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C1q/TNF-related protein-1 functions to protect against acute ischemic injury in the heart2016

    • Author(s)
      Yuasa D.,Ohashi K.,Shibata R.,Mizutani N.,Kataoka Y.,Kambara T.,Uemura Y.,Matsuo K.,Kanemura N.,Hayakawa S.,Hiramatsu-Ito M.,Ito M.,Ogawa H.,Murate T.,Murohara T. and Ouchi N.
    • Journal Title

      FASEB J

      Volume: 30 Issue: 3 Pages: 1065-1075

    • DOI

      10.1096/fj.15-279885

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeting ceramide synthase 6-dependent metastasis-prone phenotype in lung cancer cells.2016

    • Author(s)
      Suzuki M, et al.
    • Journal Title

      J. Clin. Invest.

      Volume: 126 Issue: 1 Pages: 254-265

    • DOI

      10.1172/jci79775

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased SPHK2 transcription of human colon cancer cells in serum-depleted culture: the involvement of CREB transcription factor.2015

    • Author(s)
      Mizutani N, Omori Y, Tanaka K, Ito H, Takagi A, Kojima T, Nakatochi M, Ogiso H, Kawamoto Y, Nakamura M, Suzuki M, Kyogashima M, Koizumi K, Nozawa Y, Murate T.
    • Journal Title

      J Cell Biochem

      Volume: 116 Issue: 10 Pages: 2227-2238

    • DOI

      10.1002/jcb.25173

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased Acid Ceramidase Expression depends on Upregulation of Androgen-dependent Deubiquitinases, USP2, in a Human Prostate Cancer Cell Line, LNCaP.2015

    • Author(s)
      Naoki Mizutani, Minami Inoue, Yukari Omori, Hiromi Ito, Keiko Tamiya-Koizumi, Akira Takagi, Tetsuhito Kojima, Mitsuhiro Nakamura, Soichiro Iwaki, Masahiro Nakatochi, Motoshi Suzuki, Yoshinori Nozawa, Takashi Murate
    • Journal Title

      J. Biochem.

      Volume: 印刷中 Issue: 4 Pages: 309-319

    • DOI

      10.1093/jb/mvv039

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxia remodels the composition of the constituent ceramide species of HaxCer and Hex2Cer with phytosphingosine and hydroxy fatty acids in human colon cancer LS147T cells2015

    • Author(s)
      Tanaka K.,Tamiya-Koizumi K.,Yamada M.,Murate T.,Kannagi R. and Kyogashima M.
    • Journal Title

      Glycoconj J

      Volume: 32 Pages: 615-623

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Individual profiles of free ceramide species and the constituent ceramide species of sphingomyelin and neutral glycosphingolipid and their alteration according to the sequential changes of environmental oxygen content in human colorectal cancer Caco-2 cells2014

    • Author(s)
      Tanaka, K., et al.
    • Journal Title

      Glycoconj. J.

      Volume: 31 Issue: 3 Pages: 209-219

    • DOI

      10.1007/s10719-013-9511-9

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phosphorylated Sp1 is the regulator of DNA-PKcs and DNA ligase IV transcription of daunorubicin-resistant leukemia cell lines2014

    • Author(s)
      Nishida Y, Mizutani N, Inoue M, Omori Y, Tamiya-Koizumi K, Takagi A, Kojima T, Suzuki M, Nozawa Y, Minami Y, Ohnishi K, Naoe T, Murate T.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1839 Pages: 265-274

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] メラノーマ自然発症および異色モデルマウスを用いたIL-9 の高主要効果の解析2015

    • Author(s)
      川本 義之、中山 翔太、水谷 直貴、村手 隆、武田 湖洲恵
    • Organizer
      第38回日本生化学会大会
    • Place of Presentation
      兵庫県 神戸市 神戸国際展示場
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] CERS6および癌特有のスフィンゴ脂質代謝ホメオスタシスを利用した肺がん分子標的療法2015

    • Author(s)
      鈴木 元, 村手 隆、京ヶ島 守、古水 雄志、松本 陽子、上岡 龍一、井ノ口 仁一、高橋 隆
    • Organizer
      第74回日本癌学会
    • Place of Presentation
      愛知県 名古屋市 国際会議場
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Androgen-dependent up-regulation of USP2/10 increases acid ceramidase expression in a human prostate cancer cell line, LNCaP2014

    • Author(s)
      Mizutani N. et al.
    • Organizer
      55th International Conference on the Biosciences of Lipids
    • Place of Presentation
      Aberdeen, Scotland
    • Year and Date
      2014-06-23 – 2014-06-27
    • Related Report
      2014 Research-status Report
  • [Presentation] The mechanism of cytotoxicity by resveratrol against human leukemia cello ones2014

    • Author(s)
      Omori Y. et al.
    • Organizer
      55th International Conference on the Biosciences of Lipids
    • Place of Presentation
      Aberdeen, Scotland
    • Year and Date
      2014-06-23 – 2014-06-27
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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