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Identification of the specific metabolic system for cellular senescence and tumorigenesis

Research Project

Project/Area Number 26670163
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionKyushu University (2016)
Keio University (2014-2015)

Principal Investigator

Minamishima Yoji Andrew  九州大学, 生体防御医学研究所, 特任准教授 (20593966)

Co-Investigator(Renkei-kenkyūsha) Akiko Kubo  慶應義塾大学, 医学部, 特任講師 (50455573)
Takako Hishiki  慶應義塾大学, 医学部, 特任講師 (10338022)
Yuki Sugiura  慶應義塾大学, 医学部, 特任講師 (30590202)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords細胞老化 / 代謝 / 不死化 / 癌化 / 低酸素 / 細胞周期 / メタボロミクス / 老化
Outline of Final Research Achievements

We have performed metabolome analysis on fresh, senescent, and immortalized stage in “cellular senescence to spontaneous immortalization model” using mouse embryonic fibroblasts (MEFs) 3T3 technique.
Several senescent stage-specific and immortalization-specific metabolic pathways were determined, and tetracycline-inducible tunable senescence / immortalization cellular model were under development.

Report

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

    (31 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Book (2 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Howard Hughes Medical Institute/Dana-Farber Cancer Institute/Harvard Medical School(U.S.A.)

    • Related Report
      2015 Research-status Report
  • [Journal Article] 低酸素応答による代謝制御とドラッグ・リポジショニング2017

    • Author(s)
      小柳津-寅丸智子、壽原朋宏、南嶋洋司
    • Journal Title

      Farumashia

      Volume: 53 Issue: 3 Pages: 234-237

    • DOI

      10.14894/faruawpsj.53.3_234

    • NAID

      130005398284

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of cellular energy metabolism by prolyl hydroxylase PHD2016

    • Author(s)
      南嶋洋司
    • Journal Title

      生化学

      Volume: 88 Issue: 3 Pages: 302-307

    • DOI

      10.14952/SEIKAGAKU.2016.880302

    • ISSN
      0037-1017
    • Year and Date
      2016-06-25
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acquired platinum resistance involves epithelial-to-mesenchymal transition through ubiquitin ligase FBXO32 dysregulation2016

    • Author(s)
      Tanaka N, Kosaka T, Miyazaki Y, Mikami S, Niwa N, Otsuka Y, Minamishima YA, Mizuno R, Kikuchi E, Miyajima A, Sabe H, Okada Y, Uhlen P, Suematsu M, Oya M
    • Journal Title

      JCI insight

      Volume: 1 Issue: 18

    • DOI

      10.1172/jci.insight.83654

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Obesity-induced kidney injury is attenuated by amelioration of aberrant PHD2 activation in proximal tubules2016

    • Author(s)
      Futatsugi K, Tokuyama H, Shibata S, Naitoh M, Kanda T, Minakuchi H, Yamaguchi S, Hayashi K, Minamishima YA, Yanagita M, Wakino S, Itoh H
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 365331-12

    • DOI

      10.1038/srep36533

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 敗血症における乳酸の役割 低酸素応答は血中乳酸値を下げるか?2016

    • Author(s)
      壽原朋宏、長田大雅、南嶋洋司、武田純三、森崎 浩
    • Journal Title

      臨床麻酔

      Volume: 40 Pages: 599-607

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Inhibition of the Oxygen Sensor PHD2 in the Liver Improves Survival in Lactic Acidosis by Activating the Cori Cycle2015

    • Author(s)
      Suhara T, Hishiki T, Kasahara M, Hayakawa N, Oyaizu T, Nakanishi T, Kubo A, Morisaki H, Kaelin WG Jr., Suematsu M, Minamishima YA§. (§Corresponding author)
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 112 Issue: 37 Pages: 11642-7

    • DOI

      10.1073/pnas.1515872112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Prolyl-hydroxylase PHD3 interacts with pyruvate dehydrogenase (PDH)-E1β and regulates the cellular PDH activity2014

    • Author(s)
      Kikuchi D, Minamishima YA, Nakayama K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 451 Issue: 2 Pages: 288-288

    • DOI

      10.1016/j.bbrc.2014.07.114

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 肝臓における低酸素応答を標的とした新たな乳酸アシドーシス治療法の開発 ~ Cori 回路制御機構の解明~2017

    • Author(s)
      壽原朋宏*, 菱木貴子, 笠原正貴, 早川典代, 小柳津智子, 中西豪, 久保亜紀子, 末松誠, 南嶋洋司, 森崎浩
    • Organizer
      第43回 日本集中治療医学会学術集会
    • Place of Presentation
      神戸国際展示場・神戸ポートピアホテル
    • Related Report
      2016 Annual Research Report
  • [Presentation] Targeting oxygen sensor PHD for the treatment of metformin-associated lactic acidosis (MALA)2017

    • Author(s)
      Oyaizu-Toramaru T, Suhara T, Hayakawa N, Nakamura T, Minamishima S, Kubo A, Yamaguchi K, Hishiki T, Morisaki H, Suematsu M, Minamishima YA*
    • Organizer
      Keystone Symposia “Adaptations to Hypoxia in Physiology and Disease (X4)”
    • Place of Presentation
      Whistler Conference Centre , Whistler, BC, Canada
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Targeting the oxygen sensor PHD (prolyl hydroxylase) for the treatment of lethal lactic acidosis2017

    • Author(s)
      Oyaizu-Toramaru T, Suhara T, Hayakawa N, Nakamura T, Minamishima S, Kubo A, Yamaguchi K, Hishiki T, Morisaki H, Suematsu M, Minamishima YA*
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール/長崎新聞文化ホール
    • Related Report
      2016 Annual Research Report
  • [Presentation] Glycosaminoglycan as an energy source for pancreatic cancer cells.2016

    • Author(s)
      Shotaro Kishimoto*, Yoji Andrew Minamishima*, Noriyo Hayakawa and Makoto Suematsu (*Equally contributed)
    • Organizer
      10th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics.
    • Place of Presentation
      Hyatt Regency Maui (Maui, Hawaii, U.S.A.)
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵癌細胞は間質のグリコサミノグリカンを栄養源にしている2016

    • Author(s)
      岸本翔太郎、早川典代、末松誠、南嶋洋司*
    • Organizer
      第4回がんと代謝研究会
    • Place of Presentation
      かごしま県民交流センター
    • Related Report
      2016 Annual Research Report
  • [Presentation] Prolyl hydroxylase (PHD) as a therapeutic target for metformin-associated lactic acidosis2016

    • Author(s)
      寅丸智子*、壽原朋宏、早川典代、中村貴、南嶋しづか、菱木貴子、森崎浩、末松誠、南嶋洋司
    • Organizer
      第4回低酸素研究会
    • Place of Presentation
      早稲田大学 先端生命医科学センター
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低酸素応答を標的とした各種疾患治療法の開発~致死的乳酸アシドーシスの新規治療法~2016

    • Author(s)
      小柳津-寅丸智子, 壽原朋宏, 早川典代, 中村貴, 南嶋しづか, 山口京二, 菱木貴子, 森崎浩, 末松誠, 南嶋洋司*
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 膵癌細胞は癌間質のグリコサミノグリカンをエネルギー源にしている2016

    • Author(s)
      岸本翔太郎*、早川典代、末松誠、南嶋洋司
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] 膵癌細胞は間質に豊富に存在するグリコサミノグリカンを栄養源にして いる2016

    • Author(s)
      岸本翔太郎、早川典代、末松誠、南嶋洋司*
    • Organizer
      第14回がんとハイポキシア研究会
    • Place of Presentation
      岐阜グランドホテル
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低酸素センサーPHDを標的としたメトホルミン誘発乳酸アシドーシス(MALA)治療法の開発2016

    • Author(s)
      小柳津-寅丸智子、壽原朋宏、早川典代、中村貴、南嶋しづか、山口京二、菱木貴子、森崎浩、末松誠、南嶋洋司*
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低酸素・低栄養環境下で増殖する膵管癌 (PDAC)は、間質のグリコサミノグリカン (GAG)を栄養源にしている2016

    • Author(s)
      岸本翔太郎、早川典代、末松誠、南嶋洋司*
    • Organizer
      第4回低酸素研究会
    • Place of Presentation
      早稲田大学 先端生命医科学センター
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低酸素応答によるCori回路の制御機構の解明~肝臓における低酸素応答を標的とした新たな乳酸アシドーシスの治療法の開発~2015

    • Author(s)
      壽原朋宏*、菱木貴子、笠原正貴、早川典代、小柳津智子、中西豪、久保亜紀子、森崎浩、William G. Kaelin Jr.、末松誠、南嶋洋司
    • Organizer
      BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸ポートアイランド (兵庫県神戸市)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle2015

    • Author(s)
      Tomohiro Suhara*, Takako Hishiki, Masataka Kasahara, Noriyo Hayakawa, Tomoko Oyaizu, Tsuyoshi Nakanishi, Akiko Kubo, Hiroshi Morisaki, William G. Kaelin Jr., Makoto Suematsu, Yoji Andrew Minamishima
    • Organizer
      第3回低酸素研究会
    • Place of Presentation
      早稲田大学先端生命医科学センター (東京都新宿区)
    • Year and Date
      2015-07-25
    • Related Report
      2015 Research-status Report
  • [Presentation] 低酸素応答とミトコンドリアストレス2015

    • Author(s)
      南嶋洋司*
    • Organizer
      第15回日本蛋白質科学会年会
    • Place of Presentation
      徳島市あわぎんホール (徳島県徳島市)
    • Year and Date
      2015-06-25
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 肝臓における低酸素応答はCori回路の活性化を介して血中乳酸レベルを制御している2015

    • Author(s)
      壽原朋宏、菱木貴子、笠原正貴、早川典代、小柳津智子、中西豪、久保亜紀子、森崎浩、William G. Kaelin Jr.、末松誠、南嶋洋司*
    • Organizer
      第13回がんとハイポキシア研究会
    • Place of Presentation
      国立遺伝学研究所 (静岡県三島市)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
  • [Presentation] Inactivating HIF-prolyl hydroxylase PHD2 in liver improves survival after lactic acidosis by activating Cori cycle2015

    • Author(s)
      Tomohiro Suhara, Takako Hishiki, Masataka Kasahara, Noriyo Hayakawa, Tomoko Oyaizu, Tsuyoshi Nakanishi, Akiko Kubo, Hiroshi Morisaki, Makoto Suematsu, Yoji Andrew Minamishima*
    • Organizer
      Keystone Symposia “Hypoxia: From Basic Mechanisms to Therapeutics (E3)”.
    • Place of Presentation
      Royal Dublin Society (Dublin, Ireland)
    • Year and Date
      2015-05-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 低酸素応答による乳酸代謝制御機構2014

    • Author(s)
      寿原明宏、笠原正貴、菱木貴子、早川典代、南嶋洋司、末松誠
    • Organizer
      第12回がんとハイポキシア研究会
    • Place of Presentation
      佐賀県佐賀市神野東2-5-15ホテルマリターレ創世佐賀
    • Year and Date
      2014-11-21 – 2014-11-22
    • Related Report
      2014 Research-status Report
  • [Book] 腎臓内科・泌尿器科2015

    • Author(s)
      南嶋洋司、久保亜紀子
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2015 Research-status Report
  • [Book] 実験医学増刊 Vol.32 No.15 驚愕の代謝システム メタボロームの階層から解き明かす疾患研究の新たなステージ2014

    • Author(s)
      南嶋洋司、末松 誠
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2014 Research-status Report
  • [Remarks] 新学術領域「酸素生物学」 酸素を基軸とする生命の新たな統合的理解

    • URL

      http://www.oxygenbiology.net/125071254012512.html

    • Related Report
      2015 Research-status Report
  • [Remarks] ORCID

    • URL

      http://orcid.org/0000-0001-7995-9318

    • Related Report
      2015 Research-status Report
  • [Remarks] 新学術領域「酸素生物学」

    • URL

      http://www.oxygenbiology.net/125071254012512.html

    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 乳酸アシドーシスの予防又は治療のための医薬2016

    • Inventor(s)
      南嶋洋司、寅丸智子、壽原朋宏、山口京二
    • Industrial Property Rights Holder
      南嶋洋司、寅丸智子、壽原朋宏、山口京二
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-04-08
    • Related Report
      2016 Annual Research Report

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

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