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Phosphoproteome analysis of colorectal cancer for understanding of tumor biology and its application to development of treatment

Research Project

Project/Area Number 25670572
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionKanazawa University

Principal Investigator

MINAMOTO Toshinari  金沢大学, がん進展制御研究所, 教授 (50239323)

Co-Investigator(Renkei-kenkyūsha) SUGIYAMA Naoyuki  慶應義塾大学, 政策・メディア研究科, 特任講師 (50545704)
Research Collaborator DOMOTO Takahiro  
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords大腸がん / 蛋白質リン酸化 / GSK3β
Outline of Final Research Achievements

The phosphoproteomic approach explored the putative biological mechanism by which glycogen synthase kinase (GSK)3β promotes colon cancer progression. Inhibition of GSK3β significantly modified the level of phosphorylation in a number of proteins in colon cancer cells. Integration of phosphoproteome and metabolome analysis for these proteins phosphorylated by GSK3β identified the enzyme A, a rate-limiting enzyme in glucose metabolism, which was preferentially phosphorylated by GSK3β in cancer cells. The results suggest that GSK3β promotes cancer progression by induction of aberrant glucose metabolism via phosphorylation-dependent inactivation of the enzyme A. In all, this study demonstrates that cancer treatment targeting GSK3β depends on modulation of cancer-specific profile of protein phosphorylation.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (48 results)

All 2015 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (40 results) (of which Invited: 2 results)

  • [Journal Article] Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1 and c-Jun N-terminal kinase-mediated pathway.2015

    • Author(s)
      Chikano Y, Domoto T, Furuta T, Sabit H, Kitano-Tamura A, Ilya V. Pyko, Takino T, Sai Y, Hayashi Y, Sato H, Miyamoto K, Nakada M, MinamotoT.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 14 Issue: 2 Pages: 564-574

    • DOI

      10.1158/1535-7163.mct-14-0479

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TNF-a/TNFR1 signaling promotes gastric tumorigenesis through induction of Noxo1 and Gna14 in tumor cells2014

    • Author(s)
      Oshima H, Ishikawa T, Yoshida GJ, et al.
    • Journal Title

      Oncogene

      Volume: 33 Issue: 29 Pages: 3820-3829

    • DOI

      10.1038/onc.2013.356

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lineage-specific RUNX3 hypomethylation marks the preneoplastic immune component of gastric cancer2014

    • Author(s)
      Kurklu B, Minamoto T, et al.
    • Journal Title

      Oncogene

      Volume: 印刷中 Issue: 22 Pages: 2856-66

    • DOI

      10.1038/onc.2014.233

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection and characterization of oncogene mutations in preneoplastic and early neoplastic lesions2014

    • Author(s)
      Minamoto T.
    • Journal Title

      Methods in Molecular Biology

      Volume: 1105 Pages: 381-398

    • DOI

      10.1007/978-1-62703-739-6_29

    • NAID

      120000813359

    • ISBN
      9781627037389, 9781627037396
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of angiopoietin 2 attenuates lumen formation of tumor associated vessels in vivo.2013

    • Author(s)
      Suzuki R et al.
    • Journal Title

      Int J Oncol

      Volume: 43 Issue: 5 Pages: 1447-55

    • DOI

      10.3892/ijo.2013.2076

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glycogen synthase kinase 3β inhibition sensitizes human glioblastoma cells to temozolomide by affecting O6-methylguanine DNA methyltransferase promoter methylation via c-Myc signaling2013

    • Author(s)
      Pyko IV, Nakada M, Sabit H, Teng L, Furuyama N, Hayashi Y, Kawakami K, Minamoto T, Fedulau AS, Hamada J
    • Journal Title

      Carcinogenesis

      Volume: 34 Issue: 10 Pages: 2206-2217

    • DOI

      10.1093/carcin/bgt182

    • URL

      http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aberrant glycogen synthase kinase 3β is involved in pancreatic cancer cell invasion and resistance to therapy2013

    • Author(s)
      Kitano A
    • Journal Title

      PLoS One

      Volume: 8 Issue: 2 Pages: 15-15

    • DOI

      10.1371/journal.pone.0055289

    • URL

      http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies?2012

    • Author(s)
      Loh M, Kawakami K, Minamoto T, et al
    • Journal Title

      Pharmacogenomics J

      Volume: (in press) Issue: 5 Pages: 423-429

    • DOI

      10.1038/tpj.2012.26

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1 and JNK-mediated pathway2015

    • Author(s)
      Domoto T, et al., Minamoto T.
    • Organizer
      日本癌学会シンポジウム
    • Place of Presentation
      石川県立音楽堂,金沢
    • Year and Date
      2015-01-21 – 2015-01-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Glycogen synthase kinase 3β inhibition sensitizes human glioblastoma cells to temozolomide by affecting O6-methylguanine DNA methyltransferase promoter methylation via c-Myc signaling2015

    • Author(s)
      Pyko IV, et al., Minamoto T.
    • Organizer
      日本癌学会シンポジウム
    • Place of Presentation
      石川県立音楽堂,金沢
    • Year and Date
      2015-01-21 – 2015-01-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Identification of secretory protein responsible for GEM-induced EMT in pancreatic cancer cells2015

    • Author(s)
      Shimasaki T, et al., Minamoto T.
    • Organizer
      日本癌学会シンポジウム
    • Place of Presentation
      石川県立音楽堂,金沢
    • Year and Date
      2015-01-21 – 2015-01-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大腸がんにおけるGSK3β制御性miRNAの発現と病態との関連2015

    • Author(s)
      佐々木規雄,ほか,源 利成.
    • Organizer
      日本癌学会シンポジウム
    • Place of Presentation
      石川県立音楽堂,金沢
    • Year and Date
      2015-01-21 – 2015-01-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 既存薬転用による膠芽腫のGSK3β標的療法2014

    • Author(s)
      古田拓也,源 利成,ほか.
    • Organizer
      第32回日本脳腫瘍学会学術集会
    • Place of Presentation
      シェラトン・グランデ・トウキョウベイ・ホテル,千葉浦安
    • Year and Date
      2014-11-30 – 2014-12-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] GSK3β inhibitory drugs attenuate invasion of glioblastoma cells2014

    • Author(s)
      Furuta T, Minamoto T, et al.
    • Organizer
      19th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology
    • Place of Presentation
      Loews Hotel South Beach, Miami, Florida, U. S. A.
    • Year and Date
      2014-11-13 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Identification of the GSK3β-mediated secretory protein responsible for chemotherapy-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer cells2014

    • Author(s)
      Shimasaki T, et al., Minamoto T.
    • Organizer
      The 8th International Conference of the International Society of Gastroenterological Carcinogenesis
    • Place of Presentation
      Hotel Nikko Fukuoka, Fukuoka, Japan
    • Year and Date
      2014-11-13 – 2014-11-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] Expression and clinical relevance of CRD-BP in colorectal cancer2014

    • Author(s)
      Tomita Y, et al., Minamoto T.
    • Organizer
      The 8th International Conference of the International Society of Gastroenterological Carcinogenesis
    • Place of Presentation
      Hotel Nikko Fukuoka, Fukuoka, Japan
    • Year and Date
      2014-11-13 – 2014-11-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] GSK3β阻害医薬品の膠芽腫浸潤抑制効果2014

    • Author(s)
      古田拓也,源 利成,ほか.
    • Organizer
      第73回日本脳神経外科学会学術総会
    • Place of Presentation
      グランドプリンスホテル新高輪,東京
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Involvement of GSK3β in aberrant glucose metabolism in colon cancer2014

    • Author(s)
      Domoto T, et al., Minamoto T.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Repurposing of the GSK3β-inhibiting drugs for treatment of gastrointestinal cancer2014

    • Author(s)
      Hirose M, et al., Minamoto T.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Gemcitabine triggers epithelial-mesenchymal transition (EMT)-like change and enhances cell motility in pancreatic cancer cells2014

    • Author(s)
      Shimasaki T, et al., Minamoto T.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] GSK3β阻害作用を持つ医薬品のリポジショニングによる進行膵癌の新規治療法開発2014

    • Author(s)
      島崎猛夫,源 利成,ほか.
    • Organizer
      第12回日本臨床腫瘍学会学術集会
    • Place of Presentation
      福岡国際会議場,福岡
    • Year and Date
      2014-07-17 – 2014-07-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大腸がんの糖代謝におけるGSK3βの機能解析2014

    • Author(s)
      堂本貴寛,ほか,源 利成.
    • Organizer
      第2回がんと代謝研究会
    • Place of Presentation
      東京理科大学葛飾キャンパス,東京
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular targeted therapy for osteosarcoma using glycogen synthase kinase-3 beta (GSK-3β) inhibitors2014

    • Author(s)
      Shimozaki S, Minamoto T, et al.
    • Organizer
      American Society of Clinical Oncology (ASCO) Annual Meeting 2014
    • Place of Presentation
      McCormick Place, Chicago, Illinois, U. S. A.
    • Year and Date
      2014-05-30 – 2014-06-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Phase I clinical trial of the combination therapy using gemcitabine and GSK3b inhibiting drugs for gemcitabine-resistant advanced pancreatic cancer patients2014

    • Author(s)
      Shimasaki T, Minamoto T, et al.
    • Organizer
      Digestive Disease Week (DDW) 2014
    • Place of Presentation
      McCormick Place Convention Center, Chicago, Illinois, U. S. A.
    • Year and Date
      2014-05-03 – 2014-05-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] GSK3β in cancer cell metabolism.2014

    • Author(s)
      Toshinari Minamoto
    • Organizer
      International Symposium on Tumor Biology in Kanazawa 2014 & Symposium on Drug Discovery in Academics
    • Place of Presentation
      金沢エクセルホテル東急,金沢
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Inhibition of GSK3β rectifies aberrant glucose metabolism in colon cancer cells.2014

    • Author(s)
      Takahairo Domoto, et al, Toshinari Minamoto
    • Organizer
      International Symposium on Tumor Biology in Kanazawa 2014 & Symposium on Drug Discovery in Academics
    • Place of Presentation
      金沢エクセルホテル東急,金沢
    • Related Report
      2013 Research-status Report
  • [Presentation] Therapeutic effect of the cocktail of GSK3β-inhibiting drugs against colon cancer.2014

    • Author(s)
      Mayumi Hirose, et al, Toshinari Minamoto
    • Organizer
      International Symposium on Tumor Biology in Kanazawa 2014 & Symposium on Drug Discovery in Academics
    • Place of Presentation
      金沢エクセルホテル東急,金沢
    • Related Report
      2013 Research-status Report
  • [Presentation] GSK3β is an emerging therapeutic target in pancreatic cancer: its implication for cancer cell migration and invasion.2013

    • Author(s)
      Takeo Shimasaki, Toshinari Minamoto, et al.
    • Organizer
      DDW 2013
    • Place of Presentation
      Orange County Convention Center, Orlando, FL, U.S.A.
    • Related Report
      2013 Research-status Report
  • [Presentation] GSK3β阻害作用を有する既存薬剤を用いた再発膠芽腫の免疫組織学的検討.2013

    • Author(s)
      宮下勝吉,源 利成,ほか.
    • Organizer
      第31回日本脳腫瘍病理学会
    • Place of Presentation
      FKC Hall国際ファッションセンター,東京
    • Related Report
      2013 Research-status Report
  • [Presentation] GSK3βを標的治療とした既存医薬品による膵がんの新規治療.2013

    • Author(s)
      島崎猛夫,源 利成,ほか.
    • Organizer
      第44回日本膵臓学会大会
    • Place of Presentation
      仙台国際センター,仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 大腸がんの糖代謝経路におけるGSK3βの機能解析.2013

    • Author(s)
      堂本貴寛,ほか,源 利成.
    • Organizer
      第24回日本消化器癌発生学会総会
    • Place of Presentation
      石川県立音楽堂,金沢
    • Related Report
      2013 Research-status Report
  • [Presentation] DNAメチル化パターンからみた大腸がんの特徴.2013

    • Author(s)
      小竹優範,ほか,源 利成.
    • Organizer
      第24回日本消化器癌発生学会総会
    • Place of Presentation
      石川県立音楽堂,金沢
    • Related Report
      2013 Research-status Report
  • [Presentation] 既存医薬品を用いたGSK3β阻害による大腸がん治療法の開発.2013

    • Author(s)
      廣瀬まゆみ,ほか,源 利成.
    • Organizer
      第24回日本消化器癌発生学会総会
    • Place of Presentation
      石川県立音楽堂,金沢
    • Related Report
      2013 Research-status Report
  • [Presentation] 大腸癌における核膜孔複合体因子とβ-cateninの相互作用と機能解析.2013

    • Author(s)
      藻寄 茜,源 利成,ほか.
    • Organizer
      第24回日本消化器癌発生学会総会
    • Place of Presentation
      石川県立音楽堂,金沢
    • Related Report
      2013 Research-status Report
  • [Presentation] 大腸がん細胞の糖代謝特性におけるGSK3βの病的作用.2013

    • Author(s)
      堂本貴寛,ほか,源 利成.
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] GSK3β阻害による膠芽腫のテモゾロミド増感作用とc-mycシグナルを介したMGMTプロモーターメチル化促進効果.2013

    • Author(s)
      中田光俊,源 利成,ほか.
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] GSK3β阻害作用を有する医薬品の大腸がんに対する治療効果.2013

    • Author(s)
      廣瀬まゆみ,ほか,源 利成.
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 多機能キナーゼGSK3βを標的とした膠芽腫治療の基礎と臨床.2013

    • Author(s)
      中田光俊,源 利成,ほか.
    • Organizer
      第72回日本脳神経外科学会総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] GSK3β阻害作用を有する既存薬剤を用いた再発膠芽腫治療の第I・II相臨床試験における患者背景とバイオマーカーに関する検討.2013

    • Author(s)
      宮下勝吉,源 利成,ほか.
    • Organizer
      第72回日本脳神経外科学会総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 膠芽腫マウスモデルに対する既存のGSK3β阻害医薬品の効果.2013

    • Author(s)
      古田拓也,源 利成,ほか.
    • Organizer
      第72回日本脳神経外科学会総会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 骨肉腫に対するGSK-3β阻害薬を用いた分子標的治療.2013

    • Author(s)
      下﨑真吾,源 利成,ほか.
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      幕張メッセ国際会議場,幕張,千葉
    • Related Report
      2013 Research-status Report
  • [Presentation] GSK3βを標的とする骨肉腫の新規治療法の可能性.2013

    • Author(s)
      下﨑真吾,源 利成,ほか.
    • Organizer
      第51回日本癌治療学会学術集会
    • Place of Presentation
      国立京都国際会館,京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Targeting GSK3β in colorectal and refractory cancers.2013

    • Author(s)
      Toshinari Minamoto.
    • Organizer
      7th Conference of the International Society of Gastroenterological Carcinogenesis
    • Place of Presentation
      University of Pennsylvania, Philadelphia, PA, U.S.A.
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Glycogen synthase kinase 3β promotes glioma invasion via FAK/Rac1/JNK/MMP pathway.2013

    • Author(s)
      Mitsutoshi Nakada, Toshinari Minamoto, et al.
    • Organizer
      4th Quadrennial Meeting of the World Federation of Neuro-Oncology & 18th Annual Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      Marriott Marquis Hotel, San Francisco, California, U.S.A.
    • Related Report
      2013 Research-status Report
  • [Presentation] 再発膠芽腫にGSK3β阻害作用を有する薬剤を用いた第I・II相臨床試験.2013

    • Author(s)
      宮下勝吉,源 利成,ほか.
    • Organizer
      第31回日本脳腫瘍学会
    • Place of Presentation
      フェニックス・シーガイアリゾート,宮崎
    • Related Report
      2013 Research-status Report
  • [Presentation] 膠芽腫細胞株に対するGSK3β阻害医薬品の効果解析.2013

    • Author(s)
      古田拓也,源 利成,ほか.
    • Organizer
      第31回日本脳腫瘍学会
    • Place of Presentation
      フェニックス・シーガイアリゾート,宮崎
    • Related Report
      2013 Research-status Report
  • [Presentation] DNAメチル化パターンからみた大腸がんの特徴.

    • Author(s)
      小竹優範,ほか,源 利成.
    • Organizer
      第79回大腸癌研究会
    • Place of Presentation
      梅田スカイビル,大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] 大腸癌におけるβ-cateninの転写標的CRD-BPの発現と臨床病理学的因子との比較検討.

    • Author(s)
      富田泰斗,ほか,源 利成.
    • Organizer
      第79回大腸癌研究会
    • Place of Presentation
      梅田スカイビル,大阪
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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