• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

Mechanism of metastasis inhibition by LyGDI cleaved by caspase-1

Research Project

Project/Area Number 18590706
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKanazawa Medical University

Principal Investigator

MEADA Masayo  Kanazawa Medical University, School of Medicine, Senior Assistant Professor (30199632)

Co-Investigator(Kenkyū-buntansha) OTA Takahide  Kanazawa Medical University, Medical Research Institute, Associate Professor (10152141)
Project Period (FY) 2006 – 2007
KeywordsLvGDI / RhoGDIβ / D4GDI / RhoGDI2 / Caspase-1 / Anoikis / Apoptosis / Metastasis / Colon cancer / Rho
Research Abstract

RhoGDI is a regulator for Rho family small G proteins and at least three kinds of RhoGDIs are known. LyGDI (D4GDI/RhoGDIb/RhoGDI2) is one of these RhoGDIs and characteristically has a caspase-1 cleavage site at Asp^<55>. When the expression vector of LyGDI-Δ55, which is an expected product upon cleavage by caspase-1, are introduced into metastatic mouse tumor cells (1-1src), the forced expression of LyGDI-M5 enhanced the anoikis (detachment-induced apoptosis) sensitivity and decreased the metastatic ability to the lung. Accompanied with these changes, the membrane localization of FAK (focal adhesion kinase) was decreased. LyGDI is expressed at high level in hematopoietic cells, however we found that LyGDI also expressed in several human colon cancer cell lines. Therefore, we attempted to examine the role of LyGDI-Δ55 in the anoikis in the human colon cancer cell lines. We used two cell lines, HT29 and SW480. HT29 cells are resistant to anoikis and express LyGDI at high level while SW480 cells are sensitive to anoikis and express LyGDI at low level. We examined whether LyGDI was cleaved by caspase-1 upon anoikis induction, but we could not observe the cleavage of LyGDI by caspase-1. To further confirm the cleavage of LyGDI by caspase-1 we incubated a purified human LyGDI with caspase-1 in vitro, but the cleavage of LyGDI by caspase-1 was extremely slight. These observations strongly suggested that LyGDI was not cleaved by caspase-1 at Asp^<55>. The precise cleavage site in situ is unknown, however we have found LyGDI-Δ55, which lacks a N-terminal regulating region, suppressed a metastasis. Further study of the function of LyGDI-Δ55 is continued.

  • Research Products

    (42 results)

All 2008 2007 2006

All Journal Article (10 results) (of which Peer Reviewed: 3 results) Presentation (32 results)

  • [Journal Article] Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol2008

    • Author(s)
      Maeda, M.
    • Journal Title

      Toxicology and Applied Pharmacology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol.2008

    • Author(s)
      Maeda, M.
    • Journal Title

      Toxicology and Applied Pharmacology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activation of Rac1 by Rho-guanine nucleotide dissociation inhibitor-β with defective isoprenyl-binding pocket2007

    • Author(s)
      Ota, T.
    • Journal Title

      Cell Biology International 31

      Pages: 92-96

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Activation of Rac1 by Rho-guanine nucleotide dissociation inhibitor-β with defective isoprenyl-binding pocket.2007

    • Author(s)
      Ota, T.
    • Journal Title

      Cell Biology International 31

      Pages: 92-96

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] RhoGDIβ lacking the N-terminal regulatory domain suppresses metastasis by promoting anoikis in v-src transformed cells2006

    • Author(s)
      Ota, T.
    • Journal Title

      Clinical and Experimental Metastasis 23

      Pages: 323-334

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 電離放射線マウス全身照射における各種臓器での分断化LyGDIの発現2006

    • Author(s)
      河合 秀彦
    • Journal Title

      長崎医学会雑誌 81

      Pages: 318-319

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 電離放射線誘発細胞死シグナルにおける分断化LyGDIの機能解析2006

    • Author(s)
      達家 雅明
    • Journal Title

      長崎医学会雑誌 81

      Pages: 315-317

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] RhoGDI β lacking the N-terminal regulatory domain suppresses metastasis by promoting anoikis in v-src transformed cells.2006

    • Author(s)
      Ota, T.
    • Journal Title

      Clinical and Experimental Metastasis 23

      Pages: 323-334

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Function of cleaved LyGDI in signaling pathway of cell death induced by ionizing radiation.2006

    • Author(s)
      Kawai, H.
    • Journal Title

      Nagasaki Medical Journal 81

      Pages: 315-317

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A novel bio-dosimetry system for exposure to ionizing radiation.2006

    • Author(s)
      Tatsuka, M.
    • Journal Title

      Nagasaki Medical Journal 81

      Pages: 318-319

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 低分子量G蛋白質制御因子RhoGDIβの新規電離放射線誘発切断部位の同定2007

    • Author(s)
      達家 雅明
    • Organizer
      日本放射線影響学会第50回大会
    • Place of Presentation
      千葉
    • Year and Date
      20071114-17
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Identification of a novel cleavage site of RhoGDIβ in X-irradiated BALB/c 3T3 1-1src cells2007

    • Author(s)
      Tatsuka, M.
    • Organizer
      The 50th Annual Meeting of The Japan Radiation Research Society
    • Place of Presentation
      Chiba
    • Year and Date
      20071114-17
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] v-SrcでトランスフォームしたBalb/c 3T3 A31-1-1線維芽細胞におけるアノイキス抵抗性の機構2007

    • Author(s)
      太田 隆英
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      20071003-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 転移性口腔扁平上皮癌細胞におけるエイム・ワン/オーロラBの発現とアノイキス抵抗性形質について2007

    • Author(s)
      達家 雅明
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      20071003-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Sustained phosphorylation and membrane localization of FAK is implicated in v-Src induced anoikis resistance.2007

    • Author(s)
      Ota, T.
    • Organizer
      The 66th Annual Meeting of Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      20071003-05
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] AIM-1/Aurora-B expression mediates anoikis resistance in oral suqamous cell carcinoma.2007

    • Author(s)
      Tatsuka, M.
    • Organizer
      The 66th Annual Meeting of Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      20071003-05
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Study on the damage-response signal transduction generated in egg fertilized by sperm of ionizing irradiated male parent.2007

    • Author(s)
      Kanda, A.
    • Organizer
      Hiroshima University 21st Century COE Program, Radiation Casualty Medical Research Center. The 4th International Symposium
    • Place of Presentation
      Hiroshima
    • Year and Date
      20070906-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] ヒト上皮系細胞株におけるRhoGDIβの発現と細胞内局在2007

    • Author(s)
      太田 隆英
    • Organizer
      第16回日本がん転移学会
    • Place of Presentation
      富山
    • Year and Date
      20070709-10
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] オーロラBキナーゼによるがん転移形質発現機構の解析2007

    • Author(s)
      達家 雅明
    • Organizer
      第16回日本がん転移学会
    • Place of Presentation
      富山
    • Year and Date
      20070709-10
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Expression and intracellular localization of RhoGDIβ in human epithelial cells in culture.2007

    • Author(s)
      Ota, T.
    • Organizer
      The 16th Annual Meeting of Japanese Association for Metastasis Research
    • Place of Presentation
      Toyama
    • Year and Date
      20070709-10
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Analysis of expression of metastatic phenotype by aurora-B.2007

    • Author(s)
      Tatsuka, M.
    • Organizer
      The 16th Annual Meeting of Japanese Association for Metastasis Research
    • Place of Presentation
      Toyama
    • Year and Date
      20070709-10
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Study on the damage-response signal transduction generated in egg fertilized by sperm of ionizing irradiated male parent2007

    • Author(s)
      Kanda, A.
    • Organizer
      広島大学21世紀COEプログラム第4回国際シンポジウム
    • Place of Presentation
      広島
    • Year and Date
      20070206-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 生殖細胞を介した電離放射線の被曝影響研究:ヒストンH2AXリン酸化を指標とした被曝後受精卵子内でのゲノム応答現象の解析2007

    • Author(s)
      神田 暁史
    • Organizer
      第48回原子爆弾後障害研究会
    • Place of Presentation
      広島
    • Year and Date
      2007-06-03
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Study of effect of ionizing radiation through germ cells : Analysis of genome response in fertilized egg after irradiation using phosphorylation of histone H2AX as a marker.2007

    • Author(s)
      Kanda, A.
    • Organizer
      The 48th Meeting of Japanese Society for Disorder after Atomic Bomb
    • Place of Presentation
      Hiroshima
    • Year and Date
      2007-06-03
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] がんの悪性化進展とRhoGDIβ2007

    • Author(s)
      太田 隆英
    • Organizer
      平成18年度金沢医科大学総合医学研究所研究セミナー
    • Place of Presentation
      内灘
    • Year and Date
      2007-02-03
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Progression of cancer and RhoGDIβ.2007

    • Author(s)
      Ota, T.
    • Organizer
      Research Seminar of Med. Res. Inst.
    • Place of Presentation
      Uchinada
    • Year and Date
      2007-02-03
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Caspase-1により切断されたRhoGDIβによるアノイキス抑制機構2006

    • Author(s)
      太田 隆英
    • Organizer
      第65回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      20060928-30
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 電離放射線誘発細胞死の機構に関与する低分子量G蛋白制御因子RhoGDIβ分断化産物の研究2006

    • Author(s)
      達家 雅明
    • Organizer
      第65回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      20060928-30
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] がん転移形成発現におけるオーロラB(AIM-1)の役割について2006

    • Author(s)
      神田 暁史
    • Organizer
      第65回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      20060928-30
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Mechanism of suppression of anoikis by RhoGDIβ cleaved by caspase-1.2006

    • Author(s)
      Ota, T.
    • Organizer
      The 65th Annual Meeting of Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      20060928-30
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Study of cleavage product of RhoGDIβ(a regulating factor for small G protein) involved in the process of radiation-induced cell death.2006

    • Author(s)
      Tatsuka, M.
    • Organizer
      The 65th Annual Meeting of Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      20060928-30
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Roles of aurora-B(AIM-1) in metastasis formation.2006

    • Author(s)
      Kanda, A.
    • Organizer
      The 65th Annual Meeting of Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      20060928-30
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] RhoGDIβ lacking the N-terminal regulatory domain suppresses metastasis by promoting anoikis in v-src transformed cells2006

    • Author(s)
      Ota, T.
    • Organizer
      第15回日本がん転移学会・第11回国際がん転移学会合同会議
    • Place of Presentation
      徳島
    • Year and Date
      20060903-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Expression and distribution of Aurora-B in human oral squamous cell carcinoma cell line highly metastatic to lymph node2006

    • Author(s)
      Kanda, A.
    • Organizer
      第15回日本がん転移学会・第11回国際がん転移学会合同会議
    • Place of Presentation
      徳島
    • Year and Date
      20060903-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] RhoGDIβ lacking the N-terminal regulatory domain suppresses metastasis by promoting anoikis in v-src transformed cells.2006

    • Author(s)
      Ota, T.
    • Organizer
      The 11th International Congress of Metastasis Research Society Jointed with the 15th Annual Meeting of Japanese Association for Metastasis Research
    • Place of Presentation
      Tokushima
    • Year and Date
      20060903-06
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Expression and distribution of Aurora-B in human oral squamous cell carcinoma cell line highly metastatic to lymph node.2006

    • Author(s)
      Kanda, A.
    • Organizer
      The 11th International Congress of Metastasis Research Society Jointed with the 15th Annual Meeting of Japanese Association for Metastasis Research
    • Place of Presentation
      Tokushima
    • Year and Date
      20060903-06
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 上皮細胞におけるRhoGDIβの細胞内局在の観察2006

    • Author(s)
      前田 雅代
    • Organizer
      第16回日本サイトメトリー学会
    • Place of Presentation
      長崎
    • Year and Date
      20060707-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Localization of RhoGDIβ in epithelial cells.2006

    • Author(s)
      Maeda, M.
    • Organizer
      The 16th Annual Meeting of the Japan Cytometry Society
    • Place of Presentation
      Nagasaki
    • Year and Date
      20060707-08
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 顕微鏡イメージングシステムについて2006

    • Author(s)
      太田 隆英
    • Organizer
      第2回KMU研究推進セミナー
    • Place of Presentation
      内灘
    • Year and Date
      2006-12-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Imaging system by fluorescence microscope.2006

    • Author(s)
      Ota, T.
    • Organizer
      The 2nd KMU Research Promoting Seminar
    • Place of Presentation
      Uchinada
    • Year and Date
      2006-12-01
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] RhoGDIβの分断化を指標とした新しい電離放射線バイオドジメトリー2006

    • Author(s)
      達家 雅明
    • Organizer
      第31回中国地区放射線影響研究会
    • Place of Presentation
      広島
    • Year and Date
      2006-07-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] A new biodosimetry of inonizing radiation using cleavage of RhoGDIβ as a marker.2006

    • Author(s)
      Tatsuka, M.
    • Organizer
      The 31st Annual Meeting of The Chugoku Radiation Research Society
    • Place of Presentation
      Hiroshima
    • Year and Date
      2006-07-28
    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi