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Exploring biological basis of aberrant cancer energy metabolism induced by GSK3beta toward application to cancer treatment

Research Project

Project/Area Number 17K15022
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionKanazawa University

Principal Investigator

DOMOTO TAKAHIRO  金沢大学, がん進展制御研究所, 助教 (80635540)

Research Collaborator MINAMOTO toshinari  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords分子標的治療 / がん代謝 / GSK3β / オートファジー / リン酸化
Outline of Final Research Achievements

We investigated the tumor-promoting mechanisms induced by GSK3β on energy metabolism including Warburg effect and autophagy. Aberrant GSK3β enhanced glycolysis, and led autophagic activation by induction of expression of autophagy-related transcription factors in colon cancer cells. Combined treatment with specific GSK3β inhibitor (AR-A014418) and autophagy inhibitor (hydroxychloroquine) synergistically suppressed proliferation of cancer cells. These results suggest that GSK3β is attractive candidate for cancer energy metabolism targeted therapy.

Academic Significance and Societal Importance of the Research Achievements

がんの主要エネルギー源である解糖系とオートファジーをGSK3βが統合的に制御していることが示され、GSK3β阻害によって、がん特有の代謝を一括で標的にするという独創的な治療法開発の科学的基盤になることが期待される。また、GSK3βは多彩な細胞機能を制御し、ひろく疾患に関与している。したがって、本研究の成果はがんの病態解明や医療応用に繋がることはもとより、近接領域の細胞現象への理解や他の疾患に関する治療への応用に波及する可能性がある。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (22 results)

All 2018 2017 Other

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

  • [Journal Article] Colorectal cancer cells require glycogen synthase kinase-3β for sustaining mitosis via translocated promoter region (TPR)-dynein interaction2018

    • Author(s)
      Dewi Firli R.P.、Domoto Takahiro、Hazawa Masaharu、Kobayashi Akiko、Douwaki Takayuki、Minamoto Toshinari、Wong Richard W.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 17 Pages: 13337-52

    • DOI

      10.18632/oncotarget.24344

    • NAID

      120006452368

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Novel molecular therapy targeting aberrant glycogen synthase kinase-3β in soft tissue sarcoma: a basic research2018

    • Author(s)
      Kensaku Abe, Norio Yamamoto, Takahiro Domoto, Katsuhiro Hayashi, Akihiko Takeuchi, Kentaro Igarashi, Yuta Taniguchi, Hirotaka Yonezawa, Yoshihiro Araki, Toshinari Minamoto, Hiroyuki Tsuchiya
    • Organizer
      19th EFORT Annual Congress Barcelona 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Glycogen synthase kinase (GSK) 3β induces protooncogenic autophagy in colon cancer2018

    • Author(s)
      Takahiro Domoto, Ilya V. Pyko, Dilireba Bolidong, Masahiro Uehara, Toshinari Minamoto
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Involvement of aberrant GSK3β in tumor-promoting autophagy in colorectal cancer2018

    • Author(s)
      Takahiro Domoto, Toshinari Minamoto
    • Organizer
      The 13th International Symposium of the Institute Network for Biomedical Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GSK3β participates in tumor-promoting metabolism in colon cancer2018

    • Author(s)
      Takahiro Domoto, Toshinari Minamoto
    • Organizer
      第29回日本消化器癌発生学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 膵癌細胞のエクソソーム動態の解析2017

    • Author(s)
      島崎猛夫,山本聡子,堂本貴寛,源 利成
    • Organizer
      第48回日本膵臓学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 大腸がんにおけるCRD-BPの発現とがんの臨床病理学的特性や分子病態との関連解析2017

    • Author(s)
      富田泰斗,藤井頼孝,三浦聖子,藤田 純,甲斐田大資,大西敏雄,藤田秀人,木南伸一,中野泰治,上田順彦,堂本貴寛,源 利成,小坂健夫
    • Organizer
      第72回日本消化器外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] ゲムシタビン獲得耐性膵がん細胞の幹細胞性と浸潤能におけるGSK3βの作用2017

    • Author(s)
      堂本貴寛, 竹中 哲, 宮下知治, 上原将大, 太田哲生, 源 利成
    • Organizer
      第26回日本がん転移学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵がん治療耐性に伴う幹細胞性とGSK3β/STAT3経路の機能解析2017

    • Author(s)
      竹中 哲, 宮下知治, 上原将大, 堂本貴寛, 源 利成, 太田哲生
    • Organizer
      第26回日本がん転移学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Glycogen synthase kinase (GSK)3β facilitates invasive capacity in pancreatic cancer with acquired gemcitabine resistance2017

    • Author(s)
      Takahiro Domoto, Tomoharu Miyashita, Satoshi Takenaka, Masahiro Uehara, Tetsuo Ohta, Toshinari Minamoto
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Sensitizing patient-derived glioblastoma stem-like cells to temozolomide by glycogen synthase kinase 3beta inhibition2017

    • Author(s)
      Ilya V. Pyko, Takahiro Domoto, Mitsutoshi Nakada, Toshinari Minamoto
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Aberrant glycogen synthase kinase (GSK)3β participates in proliferation of esophageal squamous cell carcinoma (ESCC)2017

    • Author(s)
      Dilireba Bolidong, Takahiro Domoto, Tomoyuki Okumura, Yoshio Endo, Masahiro Uehara, Ilya V. Pyko, Tomoharu Miyashita, Toshinari Minamoto
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Putative role of glycogen synthase kinase (GSK)-3β in acquired resistance to gemcitabine (GEM) in pancreatic cancer2017

    • Author(s)
      Masahiro Uehara, Takahiro Domoto, Satoshi Takenaka, Ilya V. Pyko, Takeo Shimasaki, Tomoharu Miyashita, Tetsuo Ohta, Toshinari Minamoto
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Influence of anti-cancer drug against exosome dynamics in pancreatic cancer cells2017

    • Author(s)
      Takeo Shimasaki, Satoko Yamamoto, Takahiro Domoto, Etsuko Kiyokawa, Tomiyasu Arisawa, Toshinari Minamoto
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Novel molecular therapy targeting aberrant GSK3beta in soft tissue sarcomas2017

    • Author(s)
      阿部健作,山本憲男,堂本貴寛,林 克洋,武内章彦,樋口貴史,谷口裕太,相羽久輝,源 利成,土屋弘行
    • Organizer
      第55回日本癌治療学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] GSK3β阻害による軟部肉腫の新しい分子標的治療2017

    • Author(s)
      阿部健作,山本憲男,堂本貴寛,林 克洋,武内章彦,樋口貴史,谷口裕太,相羽久輝,源 利成,土屋弘行
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Aberrant glycogen synthase kinase (GSK) 3β participates in tumor-promoting autophagy in colorectal cancer2017

    • Author(s)
      Takahiro Domoto, Ilya V. Pyko, Masahiro Uehara, Dilireba Bolidong, Toshinari Minamoto
    • Organizer
      第28回日本消化器癌発生学会・第9回国際消化器癌発生会議
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵がんのゲムシタビン耐性獲得におけるglycogen synthase kinase (GSK)-3βの役割2017

    • Author(s)
      上原将大, 堂本貴寛, 竹中 哲, ピコイリア, 島崎猛夫, 宮下知治, 太田哲生, 源 利成
    • Organizer
      第28回日本消化器癌発生学会・第9回国際消化器癌発生会議
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Influence of anti-cancer drug against exosome dynamics in pancreatic cancer cells2017

    • Author(s)
      Takeo Shimasaki, Satoko Yamamoto, Takahiro Domoto, Toshinari Minamoto.
    • Organizer
      第28回日本消化器癌発生学会・第9回国際消化器癌発生会議
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 肝胆膵 「膵がんの増殖,浸潤と治療不応性を繋ぐ治療標的GSK3β」2017

    • Author(s)
      島崎猛夫,堂本貴寛,宮下知治,中田光俊,元雄良治,太田哲生,源 利成
    • Total Pages
      7
    • Publisher
      アークメディア
    • Related Report
      2017 Research-status Report
  • [Remarks] 金沢大学がん進展制御研究所腫瘍制御研究分野ホームページ

    • URL

      http://ganken.cri.kanazawa-u.ac.jp/shuyoseigyo/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 金沢大学 がん進展制御研究所 腫瘍制御研究分野ホームページ

    • URL

      http://ganken.cri.kanazawa-u.ac.jp/shuyoseigyo/index.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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