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Molecular mechanisms of cancer metastasis induced by disrupting the WNK kinase mediated cytosolic Cl- homeostasis

Research Project

Project/Area Number 25460297
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Miyazaki Hiroaki  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (30360027)

Co-Investigator(Kenkyū-buntansha) MARUNAKA Yoshinori  京都府立医科大学, 大学院医学研究科, 教授 (00127036)
NIISATO Naomi  京都学園大学, 健康医療学部, 教授 (00237645)
HOSOGI Shigekuni  京都府立医科大学, 大学院医学研究科, 講師 (30433254)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords細胞内Cl-濃度 / 細胞増殖 / 細胞接着 / 細胞運動 / WNKキナーゼ / 細胞接着因子 / NKCC / KCC / Cl-チャネル
Outline of Final Research Achievements

A malignant tumor is a serious health problem because cancer cells can spread to distant parts of the body, so-called metastasis. Since metastasis is the most common cause of death from cancer, this process is an important therapeutic target. However, the molecular mechanisms of the metastasis are not fully understood. Our recent studies show that the cytosolic Cl- plays important roles in fundamental cellular functions. Thus, we investigated the effect of cytosolic Cl- concentration ([Cl-]c) on the cell proliferation, the cell migration and the cell invasion in several gastrointestinal tumor cell lines. Our study indicates that cytosolic Cl- is a key factor regulating expression of cell adhesion molecules, including E-cadherin and integrins and that cytosolic Cl- regulates WNK and Src kinase signal cascades involved in tumor proliferation, migration and invasion. These results strongly suggest that changes of [Cl-]c would play important roles in cancer development and progression.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (21 results)

All 2015 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (16 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] The voltage-gated anion channels encoded by clh-3 regulate egg laying in C. elegans by modulating motor neuron excitability2014

    • Author(s)
      Branicky R, Miyazaki H, Strange K, and Schafer WR
    • Journal Title

      Journal of Neuroscience

      Volume: 34 Issue: 3 Pages: 764-775

    • DOI

      10.1523/jneurosci.3112-13.2014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lowered extracellular pH is involved in the pathogenesis of skeletal muscle insulin resistance.2014

    • Author(s)
      Hayata H, Miyazaki H, Niisato N, Yokoyama N, Marunaka Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 445 Issue: 1 Pages: 170-174

    • DOI

      10.1016/j.bbrc.2014.01.162

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A regulatory role of K^+-Cl^- cotransporter in the cell cycle progression of breast cancer MDA-MB-231 cells.2013

    • Author(s)
      Kitagawa M, Niisato N, Shiozaki A, Ohta-Fujimoto M, Hosogi S, Miyazaki H, Ichikawa D, Otsuji E, Marunaka Y.
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 539巻 Issue: 1 Pages: 92-98

    • DOI

      10.1016/j.abb.2013.06.014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞内クロライドイオンによる細胞機能制御2015

    • Author(s)
      宮崎裕明、田中幸恵、植貴俊、塩崎敦、市川大輔、大辻英吾、中山祐治、丸中良典
    • Organizer
      膜シンポジウム2015
    • Place of Presentation
      神戸
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞内クロライドイオンによる細胞遊走制御メカニズム2015

    • Author(s)
      植貴俊、宮崎裕明、田中幸恵、中山祐治、丸中良典
    • Organizer
      第108回近畿生理談話会
    • Place of Presentation
      東大阪
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] CAL1APの同定とCALHM1/CAL1APチャネルの機能解析2015

    • Author(s)
      樽野陽幸、宮崎裕明、新里直美、孫紅昕、加塩麻紀子、丸中良典
    • Organizer
      第108回近畿生理談話会
    • Place of Presentation
      東大阪
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞内クロライドイオンによる細胞機能制御メカニズム2015

    • Author(s)
      宮崎裕明、田中幸恵、植貴俊、塩崎敦、市川大輔、大辻英吾、中山祐治、丸中良典
    • Organizer
      2015年度生理学研究所研究会『生体ホメオスタシスのgatewayとしての上皮輸送マイクロホメオスタシス機構』
    • Place of Presentation
      岡崎
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞内クロライドイオンによる神経突起伸長・膜形成制御メカニズムの解明2015

    • Author(s)
      宮崎裕明、中島謙一、丸中良典
    • Organizer
      日本膜学会37年会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞内Cl-による細胞接着因子発現制御を介した胃癌細胞浸潤・転移の分子制御機構2015

    • Author(s)
      宮崎裕明, 丸中良典
    • Organizer
      第92回日本生理学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Research-status Report
  • [Presentation] CALHMイオンチャネルの構造・機能の解析2014

    • Author(s)
      樽野陽幸, Zhong ming Ma, 新里直美, 宮崎裕明, 加塩麻紀子, 孫紅昕, Foskett J Kevin, 丸中良典
    • Organizer
      膜シンポジウム2014
    • Place of Presentation
      神戸
    • Year and Date
      2014-11-26 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Oscillatory changes in the intracellular concentration of Cl- control cell cycle progression via changes in the activity of Na+/K+/2Cl- cotransporter in MKN28 gastric cancer cells.2014

    • Author(s)
      Miyazaki, H., Tanaka, S., and Marunaka, Y.
    • Organizer
      The 2nd International Symposium on Epithelial Barrier and Transport.
    • Place of Presentation
      Kusatsu, Japan
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Lowered extracellular pH is involved in the pathogenesis of insulin resistance in skeletal muscle.2014

    • Author(s)
      Hayata, H., Miyazaki, H., and Marunaka, Y.
    • Organizer
      The 2nd International Symposium on Epithelial Barrier and Transport.
    • Place of Presentation
      Kusatsu, Japan
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] 胃癌由来MKN28細胞における細胞内Cl-濃度によるG1-S期細胞周期進行制御メカニズム2014

    • Author(s)
      宮崎裕明、丸中良典
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島大学、鹿児島
    • Related Report
      2013 Research-status Report
  • [Presentation] 細胞内クロライドイオンがリソソームpH を制御しオートファジーを制御する2014

    • Author(s)
      細木誠之、丸中良典、新里直美、楠崎克之、宮崎裕明
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島大学、鹿児島
    • Related Report
      2013 Research-status Report
  • [Presentation] 骨格筋におけるインスリン抵抗性の病態に細胞外液pH の低下が関与する2014

    • Author(s)
      早田洋樹、宮崎裕明、新里直美、横山紀子、丸中良典
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島大学、鹿児島
    • Related Report
      2013 Research-status Report
  • [Presentation] Na+/K+/2Cl-共輸送体の周期的な発現変化に伴った細胞内Cl-濃度変化が細胞周期進行を制御する2013

    • Author(s)
      宮崎裕明、丸中良典
    • Organizer
      上皮膜輸送の多層的コントロールによる生体の恒常性維持機構
    • Place of Presentation
      生理学研究所、愛知
    • Related Report
      2013 Research-status Report
  • [Presentation] CLC anion channel regulatory phosphorylation and conserved signal transduction domains2013

    • Author(s)
      Miyazaki, H., Yamada, T., Parton, A., Morrison, R., Kim, S., Beth A.H., and Strange, K.
    • Organizer
      Mechanobiology of Proteins and Cells
    • Place of Presentation
      Mount Desert Island Biological Laboratory, Bar Harbor, ME, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Na+-K+-2Cl-共輸送体(NKCC)の周期的な発現変化に伴った細胞内Cl-濃度変化による細胞周期進行制御2013

    • Author(s)
      宮崎裕明、丸中良典
    • Organizer
      膜シンポジウム2013
    • Place of Presentation
      京都府立医科大学、京都
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 骨格筋細胞におけるインスリン抵抗性への細胞外pHの関与2013

    • Author(s)
      早田洋樹、宮崎裕明、新里直美、横山紀子、丸中良典
    • Organizer
      膜シンポジウム2013
    • Place of Presentation
      京都府立医科大学、京都
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 京都府立医科大学 細胞生理学教室

    • URL

      http://kpum-molecular-cell-physiology.info/

    • Related Report
      2014 Research-status Report
  • [Remarks] 京都府立医科大学 細胞生理学

    • URL

      http://kpum-molecular-cell-physiology.info/

    • Related Report
      2013 Research-status Report

URL: 

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

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