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Identification and functional analysis of nuclear pore complex components that function to transport beta-catenin between cytoplasm and nucleus

Research Project

Project/Area Number 15K15493
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) WONG Richard  金沢大学, 自然システム系, 教授 (30464035)
ISHIGAKI Yasuhito  金沢医科大学, 総合医学研究所, 教授 (20232275)
OHTA Tetsuo  金沢大学, 医学系, 教授 (40194170)
MIYASHITA Tomoharu  金沢大学, 附属病院, 助教 (30397210)
Research Collaborator DOMOTO Takahiro  金沢大学, がん進展制御研究所, 助教 (80635540)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords大腸がん / β-カテニン / 核移送 / 核膜孔複合体
Outline of Final Research Achievements

To understand the mechanism by which β-catenin with no nuclear localization signal transits between cytoplasm and nucleus, this study investigated expression of and interaction between β-catenin and nucleoporins (Nups) that constitute nuclear pore complex and participate in nucleocytoplasmic trafficking of various functional macro-molecules. Comparative analysis of expression of 30 Nups in normal cells, colon cancer cell lines, human colorectal cancer (CRC) tissues and the non-neoplastic mucosa found an inverse association between the expression of a certain Nup (here called NupX) and the nuclear accumulation of β-catenin in colon cancer cells and CRC tissues. Subsequent analysis identified NupX among Nups coimmunoprecipitated with β-catenin and T-cell factor (Tcf)4 in protein extracts from colon cancer SW480 and HCT116 cells. Analysis of its expression and function indicated that NupX functions to excrete β-catenin from nucleus, thereby inactivating the Wnt signal pathway in CRC.

Report

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

    (31 results)

All 2017 2016 2015 2014 Other

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 4 results) Presentation (21 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Remarks (2 results)

  • [Journal Article] Nestin phosphorylation at threonies 315 and 1299 correaltes with proliferation and metastasis of human pancreatic cancer.2017

    • Author(s)
      Matsuda Y, Minamoto T, et al.
    • Journal Title

      Cancer Sci

      Volume: 108 Issue: 3 Pages: 354-361

    • DOI

      10.1111/cas.13139

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Loss of gastrokine-2 drives premalignant gastric inflammation and tumor progression.2016

    • Author(s)
      Menheniott TR, Minamoto T, et al.
    • Journal Title

      J Clin Invest

      Volume: 126 Issue: 4 Pages: 1383-400

    • DOI

      10.1172/jci82655

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficacy of glycogen synthase kinase-3β targeting against osteosarcoma via activation of β-catenin.2016

    • Author(s)
      Shimozaki S, Minamoto T, et al.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 47 Pages: 77038-51

    • DOI

      10.18632/oncotarget.12781

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Glycogen synthase kinase 3β is a pivotal mediator in cancer invasion and resistance to therapy.2016

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

      Cancer Sci

      Volume: 107 Issue: 10 Pages: 1363-72

    • DOI

      10.1111/cas.13028

    • NAID

      120005895690

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Long interspersed nucleotide element-1 methylation: a determinant of response to chemotherapy and prognosis in advanced-stage colorectal cancer.2016

    • Author(s)
      Kaneko M, et al., Minamoto T.
    • Journal Title

      BMC Cancer

      Volume: 16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 有糸分裂期の機能性ヌクレオポリン:大腸がんの病態解明と治療への応用2016

    • Author(s)
      橋爪智恵子,源 利成,Richard Wong.
    • Journal Title

      生化学

      Volume: 88 Pages: 748-51

    • NAID

      120006464083

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [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
      2015 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
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 大腸がんWnt経路研究から同定した治療標的GSK3β:難治,希少がんへの展開2017

    • Author(s)
      源 利成
    • Organizer
      埼玉大腸がん地域連携キャンサーボード
    • Place of Presentation
      ラ・ボア・ラクテ,川越
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 消化器・難治がんの糖代謝特性と治療:創薬標的GSK3βに着目して2017

    • Author(s)
      源 利成
    • Organizer
      第4回山梨医学フォーラム
    • Place of Presentation
      山梨大学医学部,山梨県中央市
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 膠芽腫に対するテモゾロミド併用GSK3β標的療法.2016

    • Author(s)
      古田拓也,源 利成,ほか
    • Organizer
      第34回日本脳腫瘍学会学術集会
    • Place of Presentation
      甲府富士屋ホテル,甲府
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] GSK3β阻害による軟部肉腫の治療効果の検討.2016

    • Author(s)
      阿部健作,源 利成,ほか
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場,福岡
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] GSK3βはがん促進性オートファジーを介して大腸がん細胞の生存に関与する.2016

    • Author(s)
      堂本貴寛,ほか,源 利成
    • Organizer
      第75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
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Sensitizing patient-derived glioblastoma stem-like cells to temozolomide by glycogen synthase kinase 3β inhibition.2016

    • Author(s)
      Pyko IV, et al., Minamoto T.
    • Organizer
      第75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
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 膵がんの化学療法耐性獲得にけるglycogen synthase kinase (GSK)-3βの役割.2016

    • Author(s)
      上原将大,ほか,源 利成
    • Organizer
      第75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
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 膵癌細胞のエクソソーム動態に影響する因子の検討.2016

    • Author(s)
      島崎猛夫,ほか,源 利成
    • Organizer
      第75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
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] TJ-14による食道発癌抑制とその機序.2016

    • Author(s)
      宮下知治,源 利成,ほか
    • Organizer
      第75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
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 膵癌細胞のエクソソーム動態に影響する因子の検討.2016

    • Author(s)
      島崎猛夫,ほか,源 利成
    • Organizer
      第27回日本消化器癌発生学会総会
    • Place of Presentation
      城山観光ホテル,鹿児島
    • Year and Date
      2016-09-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] GSK3βを阻害することによる膵臓がんの化学療法耐性解除への可能性.2016

    • Author(s)
      竹中 哲,ほか,源 利成
    • Organizer
      25回日本がん転移学会学術集会・総会
    • Place of Presentation
      米子コンベンションセンター,米子
    • Year and Date
      2016-07-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Down modulation of glycogen synthase kinase (GSK)-3β disrupts Translocated Promoter Region (Tpr)-dynein axis during mitosis in colon cancer cells.2016

    • Author(s)
      Dewi FRP, Minamoto T, et al.
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ,京都
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 抗がん剤により膵がん細胞に誘導される分子とエクソソームを介した細胞間相互作用の解析2015

    • Author(s)
      島崎猛夫,山本聡子,源 利成
    • Organizer
      第26回日本消化器癌発生学会総会
    • Place of Presentation
      米子全日空ホテル,米子
    • Year and Date
      2015-11-19
    • Related Report
      2015 Research-status Report
  • [Presentation] GSK3β阻害薬を用いた骨肉腫への分子標的治療2015

    • Author(s)
      下崎真吾,源 利成,ほか
    • Organizer
      第53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
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
  • [Presentation] GSK3βはFAK/Rac1/ JNK経路を介するMMPsの発現亢進によって膠芽腫細胞の浸潤を推進する2015

    • Author(s)
      堂本貴寛,ほか,源 利成
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場,名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] ゲムシタビンにより膵癌細胞に誘導されるEMT促進因子の同定と機能解析:GSK3β阻害による制御2015

    • Author(s)
      島崎猛夫,ほか,源 利成
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場,名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] エクソソームを介する癌細胞間相互作用:新しい培養プレートによる解析2015

    • Author(s)
      山本聡子,源 利成,ほか
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場,名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Biological basis of cancer treatment by GSK3β inhibition2015

    • Author(s)
      Minamoto T
    • Organizer
      International Symposium on Tumor Biology in Kanazawa
    • Place of Presentation
      金沢大学十全記念館,金沢
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 既存薬転用を応用した膠芽腫に対するGSK3β標的治療2015

    • Author(s)
      古田拓也,源 利成,ほか
    • Organizer
      第16回日本分子脳神経外科学会
    • Place of Presentation
      アクトシティ浜松コングレスセンター,浜松
    • Year and Date
      2015-08-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 大腸がん糖代謝特性におけるGSK3βの役割2015

    • Author(s)
      堂本貴寛,ほか,源 利成
    • Organizer
      第3回がんと代謝研究会
    • Place of Presentation
      石川県立音楽堂,金沢
    • Year and Date
      2015-07-16
    • Related Report
      2015 Research-status Report
  • [Presentation] 抗癌剤により膵癌細胞に誘導されるEMT促進因子の同定と機能解析:GSK3β阻害による制御2015

    • Author(s)
      島崎猛夫,源 利成,ほか
    • Organizer
      第46回日本膵臓学会大会
    • Place of Presentation
      名古屋国際会議場,名古屋
    • Year and Date
      2015-06-19
    • Related Report
      2015 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

    • URL

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

    • Related Report
      2016 Annual Research Report
  • [Remarks] 金沢大学がん進展制御研究所腫瘍制御

    • URL

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

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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