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Regulation of membrane domain functions by lipid transport and lipid metabolism in cancer cells

Research Project

Project/Area Number 16K08618
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Yamauchi Yoshio  東京大学, 大学院農学生命科学研究科(農学部), 准教授 (00444878)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords脂質代謝 / 細胞内輸送 / コレステロール / スフィンゴ脂質 / 細胞内脂質輸送 / がん / 膜ドメイン / 脂質輸送 / 癌 / 脂質 / 発現制御 / 代謝
Outline of Final Research Achievements

Lipid rafts, membrane domains rich in cholesterol and sphingolipids, play diverse and important roles in malignant properties of cancer cells. However, a regulatory mechanism for functions of the membrane domains remains poorly understood. In this work, we studied mechanisms by which intracellular lipid transport and lipid metabolism cooperatively regulate functionality of lipid rafts in cancer cells. Our results showed that intracellular transport of cholesterol and sphingolipids regulates lipid biosynthesis and integrity of lipid rafts, supporting malignant properties of cancer cells.

Academic Significance and Societal Importance of the Research Achievements

がん細胞では特徴的な代謝変化がしばしば認められ、この性質はがん細胞の悪性形質に深く関与している。がん細胞における脂質合成の亢進は、このような代謝的な特徴の一つである。また、オンコジェニックシグナルの活性化において、脂質ラフトと呼ばれるコレステロールおよびスフィンゴ脂質を豊富に含む膜ドメインが重要な役割を果たしている。本研究課題では、コレステロールを中心とする脂質合成と脂質ラフト構成脂質の細胞内輸送が膜ドメイン機能を調節していることを明らかにし、がん細胞における脂質代謝の重要性の一端を明らかにした。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (30 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results)

  • [Int'l Joint Research] Harvard University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] ダートマス大学(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] ダートマス大学/イリノイ大学(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP2020

    • Author(s)
      Kuan Yen-Chou、Takahashi Yu、Maruyama Takashi、Shimizu Makoto、Yamauchi Yoshio、Sato Ryuichiro
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 12 Pages: 3918-3928

    • DOI

      10.1074/jbc.ra119.011849

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bridging molecules are secreted from the skeletal muscle and potentially regulate muscle differentiation2020

    • Author(s)
      Chikazawa Miho、Shimizu Makoto、Yamauchi Yoshio、Sato Ryuichiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 522 Issue: 1 Pages: 113-120

    • DOI

      10.1016/j.bbrc.2019.11.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sterol Metabolism and Transport in Atherosclerosis and Cancer2018

    • Author(s)
      Yamauchi Yoshio、Rogers Maximillian A.
    • Journal Title

      Frontiers in Endocrinology

      Volume: 9

    • DOI

      10.3389/fendo.2018.00509

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Methods for Monitoring ABCA1-Dependent Sterol Release2017

    • Author(s)
      Yamauchi Y, Yokoyama S, Chang TY
    • Journal Title

      Methods Mol Biol

      Volume: 1583 Pages: 257-273

    • DOI

      10.1007/978-1-4939-6875-6_19

    • ISBN
      9781493968732, 9781493968756
    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cellular Cholesterol Homeostasis in Alzheimer's Disease2017

    • Author(s)
      Chang TY, Yamauchi Y, Hasan M, Chang CC
    • Journal Title

      J Lipid Res

      Volume: 印刷中 Issue: 12 Pages: 2239-2254

    • DOI

      10.1194/jlr.r075630

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Raft-based interactions of gangliosides with a GPI-anchored receptor2016

    • Author(s)
      N. Komura, K. G. N. Suzuki, H. Ando, M. Konishi, M. Koikeda, A. Imamura, R. Chadda, T. K. Fujiwara, H. Tsuboi, R. Sheng, W. Cho, K. Furukawa, K. Furukawa, Y. Yamauchi, H. Ishida, A. Kusumi (Co-Corresponding Author), and M. Kiso
    • Journal Title

      Nat. Chem. Biol.

      Volume: in press Issue: 6 Pages: 402-410

    • DOI

      10.1038/nchembio.2059

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression analysis of 0-series gangliosides in human cancer cell lines with monoclonal antibodies generated using knockout mice of ganglioside synthase genes2016

    • Author(s)
      Bhuiyan RH, Kondo Y, Yamaguchi T, Tokuda N, Ohkawa Y, Hashimoto N, Ohmi Y, Yamauchi Y, Furukawa K, Okajima T, Furukawa K
    • Journal Title

      Glycobiology

      Volume: 26 Issue: 9 Pages: 984-998

    • DOI

      10.1093/glycob/cww049

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased expression levels of ppGalNAc-T13 in lung cancers: Significance in the prognostic diagnosis2016

    • Author(s)
      Nogimori K, Hori T, Kawaguchi K, Fukui T, Mii S, Nakada H, Matsumoto Y, Yamauchi Y, Takahashi M, Furukawa K, Tetsuya O, Yokoi K, Hasegawa Y, Furukawa K
    • Journal Title

      Int J Oncol

      Volume: 49 Issue: 4 Pages: 1369-1376

    • DOI

      10.3892/ijo.2016.3638

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of B4GALNT1, an essential glycosyltransferase for the synthesis of complex gangliosides, suppresses BACE1 degradation and modulates APP processing2016

    • Author(s)
      Yamaguchi T, Yamauchi Y, Furukawa K, Ohmi Y, Ohkawa Y, Zhang Q, Okajima T, Furukawa K
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 34505-34505

    • DOI

      10.1038/srep34505

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 骨格筋障害・萎縮におけるABCA1遺伝子発現応答の解析2020

    • Author(s)
      小野敦子、清水誠、近澤未歩、山内祥生、佐藤隆一郎
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] コレステロール恒常性維持機構とその生理的な役割2019

    • Author(s)
      山内祥生
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Role of endogenous oxysterols in cellular cholesterol homeostasis2019

    • Author(s)
      Yoshio Yamauchi, Hodaka Saito, Ryuichiro Sato
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of cellular sterol homeostasis by endogenous oxysterols2019

    • Author(s)
      山内祥生
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 細胞内で産生された酸化ステロールによるコレステロール代謝制御2019

    • Author(s)
      齋藤穂高、佐藤隆一郎、山内祥生
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂質代謝制御因子Insigを介した酸化ステロールによる新規応答2019

    • Author(s)
      渡邉雄一、三吉翔子、清水誠、山内祥生、佐藤隆一郎
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] mTORシグナルによるコレステロール代謝調節機構2018

    • Author(s)
      山内祥生、佐藤隆一、古川鋼一
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Sterol flux at the plasma membrane and sterol sensing at the ER2018

    • Author(s)
      山内祥生
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 細胞ステロールセンシング:制御機構とその異常2018

    • Author(s)
      山内祥生
    • Organizer
      第102回日本栄養・食糧学会関東支部シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 内因性酸化ステロールによるコレステロール代謝制御機構に及ぼす影響2018

    • Author(s)
      齋藤穂高、山内祥生、佐藤隆一郎
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] SREBP-SCAP相互作用部位の解析2018

    • Author(s)
      丸山貴史、官産州、清水誠、山内祥生、佐藤隆一郎
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 内因性酸化ステロールによるコレステロール恒常性制御2018

    • Author(s)
      齋藤穂高、山内祥生、佐藤隆一郎
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] mTORシグナルによるSREBP活性化機序の解析2018

    • Author(s)
      山内祥生、古川鋼一、佐藤隆一郎
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 内因性酸化ステロールがSREBP-2活性に及ぼす影響2018

    • Author(s)
      齋藤穂高、山内祥生、佐藤隆一郎
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 骨格筋萎縮時に発現誘導されるAnkrd1の機能解析2018

    • Author(s)
      吉田壮志、橋詰力、清水誠、井上順、山内祥生、佐藤隆一郎
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ABCA1依存的HDL形成におけるステロール分子特異性と膜ドメイン2017

    • Author(s)
      山内祥生、横山信治,Ta-Yuan Chang
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都女子大学、京都府京都市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] がん細胞におけるlipogenic phenotypeの重要性とその制御機構2017

    • Author(s)
      山内祥生
    • Organizer
      第59回日本脂質生化学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] SREBPプロセシングを阻害する新規低分子量化合物によって明らかになったヒトメラノーマ細胞におけるSREBP依存的なメバロン酸経路の重要性,ポスター2016

    • Author(s)
      山内祥生,太田晃成,渡邉瑞貴,五十嵐政智,佐藤隆一郎,上杉志成,古川鋼一
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜、神奈川県横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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