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The molecular mechanism of a lipid mediator involved in metabolic dynamics of breast cancer

Research Project

Project/Area Number 15K15471
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionNiigata University

Principal Investigator

Nagahashi Masayuki  新潟大学, 医歯学総合病院, 講師 (30743918)

Co-Investigator(Kenkyū-buntansha) 西條 康夫  新潟大学, 医歯学系, 教授 (10270828)
小山 諭  新潟大学, 医歯学系, 教授 (10323966)
小杉 伸一  新潟大学, 医歯学総合病院, 特任教授 (90401736)
小林 隆  新潟大学, 医歯学総合病院, 講師 (40464010)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脂質メディエーター / スフィンゴシン-1-リン酸 / スフィンゴシンキナーゼ / 癌代謝 / メタボローム / CRISPR/Cas9 / 薬剤耐性 / 乳癌
Outline of Final Research Achievements

A pleiotropic bioactive lipid mediator, sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphK1 and SphK2) regulates many physiological and pathological processes. We hypothesized that SphKs regulates cancer cell-specific metabolism, which related to the cancer cell proliferation and survival. Metabolomics profiles of both SphK1KO and SphK2KO breast cancer cells were dramatically changed in the glycolysis pathway and TCA cycle compared to the control cells. Our data suggests that SphKs play an important role in cancer specific metabolism.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (30 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (17 results) (of which Int'l Joint Research: 9 results)

  • [Int'l Joint Research] ロズウェルパーク癌研究所/バージニア州立大学(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] バージニア州立大学/ロズウェルパーク癌研究所(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Virginia Commonwealth University(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Ceramide species are elevated in human breast cancer and are associated with less aggressiveness2018

    • Author(s)
      Moro K, Kawaguchi T, Tsuchida J, Gabriel E, Qi Q, Yan L, Wakai T, Takabe K, Nagahashi M
    • Journal Title

      Oncotarget

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice2017

    • Author(s)
      Wang Y, Aoki H, Yang J, Peng K, Liu R, Li X, Qiang X, Sun L, Gurley EC, Lai G, Zhang L, Liang G, Nagahashi M, Takabe K, Pandak WM, Hylemon PB, Zhou H.
    • Journal Title

      Hepatology

      Volume: 印刷中 Issue: 6 Pages: 2005-2018

    • DOI

      10.1002/hep.29076

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Doxorubicin effect is enhanced by sphingosine-1-phosphate signaling antagonist in breast cancer2017

    • Author(s)
      Katsuta Eriko、Yan Li、Nagahashi Masayuki、Raza Ali、Sturgill Jamie L.、Lyon Debra E.、Rashid Omar M.、Hait Nitai C.、Takabe Kazuaki
    • Journal Title

      Journal of Surgical Research

      Volume: 219 Pages: 202-213

    • DOI

      10.1016/j.jss.2017.05.101

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Bile acids as global regulators of hepatic nutrient metabolism.2017

    • Author(s)
      Hylemon PB, Takabe K, Dozmorov M, Nagahashi M, Zhou H
    • Journal Title

      Liver Res.

      Volume: 1 Issue: 1 Pages: 10-16

    • DOI

      10.1016/j.livres.2017.03.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The roles of bile acids and sphingosine-1-phosphate signaling in the hepatobiliary diseases.2016

    • Author(s)
      Nagahashi M, Yuza K, Hirose Y, Nakajima M, Ramanathan R, Hait NC, Hylemon PB, Zhou H, Takabe K, Wakai T.
    • Journal Title

      J Lipid Res.

      Volume: 57 Issue: 9 Pages: 1636-43

    • DOI

      10.1194/jlr.r069286

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] DNA damage response and sphingolipid signaling in liver diseases2016

    • Author(s)
      Nagahashi M, Matsuda Y, Moro K, Tsuchida J, Soma D, Hirose Y, Kobayashi T, Kosugi SI, Takabe K, Komatsu M, Wakai T
    • Journal Title

      Surg Today

      Volume: 印刷中 Issue: 9 Pages: 995-1005

    • DOI

      10.1007/s00595-015-1270-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 脂質メディエーターを介した胆汁酸シグナル伝達系の役割2016

    • Author(s)
      永橋 昌幸,大橋 拓,滝沢 一泰,坂田 純,小林 隆,若井 俊文
    • Journal Title

      胆道

      Volume: 30 Pages: 220-227

    • NAID

      130005157398

    • Related Report
      2016 Research-status Report
  • [Journal Article] Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer.2016

    • Author(s)
      Moro K, Nagahashi M, Ramanathan R, Takabe K, Wakai T.
    • Journal Title

      World J Clin Cases.

      Volume: 4 Issue: 7 Pages: 155-64

    • DOI

      10.12998/wjcc.v4.i7.155

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] DNA damage response and sphingolipid signaling in liver diseases.2016

    • Author(s)
      Masayuki Nagahashi, Yasunobu Matsuda, Kazuki Moro, Daiki Soma, Junko Tsuchida, Yuki Hirose, Takashi Kobayashi, Shin-ichi Kosugi, Kazuaki Takabe, Masaaki Komatsu, Toshifumi Wakai
    • Journal Title

      Surgery Today

      Volume: 未定

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 脂質メディエーターを介した胆汁酸シグナル伝達系の役割2016

    • Author(s)
      永橋昌幸, 大橋拓, 滝沢一泰, 坂田純, 小林隆, 若井俊文
    • Journal Title

      胆道

      Volume: 未定

    • NAID

      130005157398

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Breast Cancer Cell Metabolism Is Regulated by Sphingosine Kinases2018

    • Author(s)
      Nagahashi M, Nakajima M, Abe M, Saito T, Komatsu M, Soga T, Tsuchida J, Yuza K, Takabe K, Sakimura K, Wakai T
    • Organizer
      The 13th Annual Academic Surgical Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ceramide species are elevated with activation of ceramide biosynthesis pathways in human breast cancer2018

    • Author(s)
      Moro K, Kawaguchi T, Tsuchida J, Gabriel E, Qi Q, Yan L, Sato N, Wakai T, Takabe K, Nagahashi M
    • Organizer
      The 13th Annual Academic Surgical Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression of Phosphorylated Sphingosine Kinase 1 Is Associated with Invasiveness of Gastric Cancer.2017

    • Author(s)
      Hanyu T, Ichikawa H, Ishikawa T, Kosugi S, Nakajima M, Sakata J, Kobayashi T, Kameyama H, Wakai T, Nagahashi M
    • Organizer
      The 12th Annual Academic Surgical Congress
    • Place of Presentation
      Las Vegas, USA
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sphingosine Kinase 1 Contributes to Breast Cancer Cell Metabolism and Survival.2017

    • Author(s)
      Nagahashi M, Nakajima M, Saito T, Komatsu M, Soga T, Zhao R, Zhou H, Okuda S, Takabe K, Wakai T
    • Organizer
      The 12th Annual Academic Surgical Congress
    • Place of Presentation
      Las Vegas, USA
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Obesity-induced Sphingosine-1-phosphate in Breast Cancer Interstitial Fluid Promotes Angiogenesis.2017

    • Author(s)
      Tsuchida J, Nakajima M, Moro K, Ohtani A, Endo M, Niwano T, Tatsuda K, Toshikawa C, Hasegawa M, Ikarashi M, Koyama Y, Sakata J, Kobayashi T, Kameyama H, Wakai T, Takabe K, Nagahashi M
    • Organizer
      The 12th Annual Academic Surgical Congress
    • Place of Presentation
      Las Vegas, USA
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of Sphingosine-1-Phosphate Produced by Sphingosine Kinases in Pancreatic Cancer Progression2017

    • Author(s)
      Nakajima M, Miura Y, Ando T, Yuza K, Tsuchida J, Tajima Y, Abe M, Sakimura K, Wakai T, Nagahashi M
    • Organizer
      The 12th Annual Academic Surgical Congress
    • Place of Presentation
      Las Vegas, USA
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 乳癌および周囲微小環境では高濃度のセラミドが産生される2017

    • Author(s)
      諸 和樹,永橋昌幸,遠藤麻巳子,大溪彩香,土田純子,庭野稔之,辰田久美子,長谷川美樹,利川千絵,五十嵐麻由子,中島真人,小山 諭,坂田 純,亀山仁史,小林 隆,高部和明,若井俊文
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 乳癌細胞の代謝動態におけるスフィンゴシン-1-リン酸産生酵素の働き2017

    • Author(s)
      永橋昌幸,中島真人,土田純子,諸 和樹,遠藤麻巳子,大渓彩香,庭野稔之,辰田久美子,長谷川美樹,利川千絵,五十嵐麻由子,坂田 純,亀山仁史,小林 隆,高部和明,斎藤哲也,小松雅明,曽我朋義,小山 諭,若井俊文
    • Organizer
      第24回外科侵襲とサイトカイン研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Sphingosine-1-phosphate and tumor-associated immune cells in the tumor microenvironment2017

    • Author(s)
      Tsuchida J, Nagahashi M, Nakajima M, Takabe K, Wakai T
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肥満を伴う乳癌患者における血清スフィンゴシン-1-リン酸の定量2016

    • Author(s)
      土田 純子、永橋 昌幸、遠藤 麻巳子、大溪 彩香、庭野 稔之、辰田 久美子、利川 千絵、長谷川 美樹、五十嵐 麻由子、小山 諭、高部 和明、若井 俊文
    • Organizer
      第78回臨床外科学会総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都港区)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 肥満によって促進される乳癌の血管新生に対する抗スフィンゴシン-1-リン酸受容体治療2016

    • Author(s)
      永橋 昌幸,大渓 彩香,遠藤 麻巳子,土田 純子,諸 和樹,庭野 稔之,辰田 久美子,利川 千絵,長谷川 美樹,五十嵐 麻由子,中島 真人,小山 諭,山田 顕光,青柳 智義,高部 和明,若井 俊文
    • Organizer
      第24回日本乳癌学会学術総会
    • Place of Presentation
      東京ビックサイト(東京都江東区)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 乳がん手術検体におけるスフィンゴリン脂質の定量2016

    • Author(s)
      中島 真人,永橋 昌幸,大渓 彩香,遠藤 麻巳子,土田 純子,諸 和樹,庭野 稔之,辰田 久美子,利川 千絵,長谷川 美樹,五十嵐 麻由子,小山 諭,若井 俊文
    • Organizer
      第24回日本乳癌学会学術総会
    • Place of Presentation
      東京ビックサイト(東京都江東区)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Dysregulation of Sphingolipids in Human Breast Cancer2016

    • Author(s)
      Masayuki Nagahashi, Junko Tsuchida, Kazuki Moro, Toshiyuki Niwano, Kumiko Tatsuda, Chie Toshikawa, Miki Hasegawa, Yu Koyama, Takashi Kobayashi, Shin-ichi Kosugi, Hitoshi Kameyama, Hiroaki Aoki, Kazuaki Takabe, Toshifumi Wakai
    • Organizer
      The 11th Annual Academic Surgical Congress
    • Place of Presentation
      Jacksonville, USA
    • Year and Date
      2016-02-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Serum sphingosine-1-phosphate levels are elevated in breast cancer patients with lymph node metastasis2016

    • Author(s)
      Junko Tsuchida, Masayuki Nagahashi, Kazuki Moro, Toshiyuki Niwano, Kumiko Tatsuda, Chie Toshikawa, Miki Hasegawa, Yu Koyama, Takashi Kobayashi, Shin-ichi Kosugi, Hitoshi Kameyama, Hiroaki Aoki, Kazuaki Takabe, Toshifumi Wakai
    • Organizer
      The 11th Annual Academic Surgical Congress
    • Place of Presentation
      Jacksonville, USA
    • Year and Date
      2016-02-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Obesity increases the lipid mediator, sphingosine-1-phosphate in the tumor and tumor microenvironment, and promotes tumor progression2015

    • Author(s)
      Junko Tsuchida, Masayuki Nagahashi, Kazuki Moro, Kumiko Tatsuda, Yu Koyama, Kazuaki Takabe, Toshifumi Wakai
    • Organizer
      San Antonio Breast Cancer Symposium 2015
    • Place of Presentation
      San Antonio, USA
    • Year and Date
      2015-12-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 胆汁酸はスフィンゴシン-1-リン酸シグナル伝達系を介して 肝臓における脂質代謝を調節している2015

    • Author(s)
      永橋 昌幸,廣瀬 雄己,須藤 翔,大橋 拓,滝沢 一泰,高野 可赴,坂田 純,小林 隆,若井 俊文
    • Organizer
      第51日本胆道学会学術集会
    • Place of Presentation
      ホテル東日本宇都宮(栃木県宇都宮市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
  • [Presentation] Specific inhibitor of a bioactive lipid mediator suppresses breast cancer-induced angiogenesis and lymphangiogenesis2015

    • Author(s)
      Masayuki Nagahashi, Kazuki Moro, Junko Tsuchida, Kumiko Tatsuda, Chie Toshikawa, Miki Hasegawa, Yoshifumi Shimada, Kazuaki Takabe, Yasuo Saijo, Toshifumi Wakai
    • Organizer
      第13回日本臨床腫瘍学会学術集会
    • Place of Presentation
      ロイトン札幌(北海道札幌市)
    • Year and Date
      2015-07-16
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-01-27  

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