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A new role of podosome formation as a mediator of cell-cell fusion

Research Project

Project/Area Number 23689020
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionHokkaido University (2013)
Keio University (2011-2012)

Principal Investigator

OIKAWA Tsukasa  北海道大学, 医学(系)研究科(研究院), 特任講師 (20457055)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000)
Fiscal Year 2013: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2012: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2011: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords細胞融合 / 細胞極性 / 上皮ー間葉転換 / ポドソーム / 破骨細胞 / がん細胞 / 浸潤
Research Abstract

Cell-cell fusion requires dynamic rearrangement of the plasma membrane and cytoskeleton, and this process involves numerous previously characterized factors. However, the mechanisms and consequences of cell-cell fusion remains obscure. This study revealed that an adaptor protein Tks5 is essential for both formation of circumferential podosomes and osteoclast fusion without altering osteoclast differentiation. As Tks5 is known to promote the formation of invadopodia in cancer cells, I tested if these cells also have the potential to fuse with osteoclasts. Among the cells tested, B16F0 melanoma cells formed circumferential invadopodia with Tks5 accumulation. Co-culture of B16F0 melanoma cells with osteoclasts in an inflammatory milieu promoted increased formation of melanoma-osteoclast hybrid cells. These results revealed a previously unknown mechanism of regulation of both circumferential podosomes/invadopodia formation and cell-cell fusion by Tks5.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (26 results)

All 2013 2012 2011 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (17 results) (of which Invited: 2 results) Remarks (4 results)

  • [Journal Article] Acquired expression of NFATc1 downregulates E-cadherin and promotes cancer cell invasion.2013

    • Author(s)
      Oikawa T
    • Journal Title

      Cancer Res

      Volume: 73 Issue: 16 Pages: 5100-5109

    • DOI

      10.1158/0008-5472.can-13-0274

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] IRSp53 mediates podosome formation via VASP in NIH-Src cells2013

    • Author(s)
      Oikawa T, Okamura H, Dietrich F, Senju Y, Takenawa T, Suetsugu S
    • Journal Title

      PLoS ONE

      Volume: 8(3) Issue: 3 Pages: e60528-e60528

    • DOI

      10.1371/journal.pone.0060528

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of osteoclasts by membrane-derived lipid mediators2013

    • Author(s)
      Oikawa T, Kuroda Y, Matsuo K
    • Journal Title

      Cell Mol Life Sci

      Volume: 70(18) Issue: 18 Pages: 3341-3353

    • DOI

      10.1007/s00018-012-1238-4

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible role of IRTKS in Tks5-driven osteoclast fusion2012

    • Author(s)
      Oikawa T and Matsuo K
    • Journal Title

      Commun Integr Biol

      Volume: 5(5) Issue: 5 Pages: 511-515

    • DOI

      10.4161/cib.21252

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion.2012

    • Author(s)
      Oikawa T, Oyama M, Kozuka-Hata H, Uehara S, Udagawa N, Saya H, and Matsuo K.
    • Journal Title

      J Cell Biol

      Volume: 197 Issue: 4 Pages: 553-568

    • DOI

      10.1083/jcb.201111116

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] がん−マクロファージ細胞融合による、がん悪性化機構の解析2013

    • Author(s)
      及川司
    • Organizer
      第2回蛍光バイオイメージングミニシンポジウム
    • Place of Presentation
      北海道大学電子科学研究所(札幌市)
    • Year and Date
      2013-09-20
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] アダプター分子Tks5依存的なポドソーム/インベードポディア形成と、これを介した破骨/がん細胞融合の解析2013

    • Author(s)
      及川司,尾山大明,秦裕子,中村敦子,大西伸幸,上原俊介,宇田川信之,山田健人,佐谷秀行,松尾光一
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市)(口頭発表・シンポジウム)
    • Related Report
      2013 Final Research Report
  • [Presentation] アダプター分子Tks5依存的なポドソーム/インベードポディア形成と、これを介した破骨/がん細胞融合の解析2013

    • Author(s)
      及川 司、尾山大明、秦 裕子、中村敦子、大西信幸、上原俊介、宇田川信之、山田健人、佐谷秀行、松尾光一
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] がん-マクロファージ細胞融合による、がん悪性化機構の解析2013

    • Author(s)
      及川 司
    • Organizer
      第2回蛍光バイオイメージングミニシンポジウム
    • Place of Presentation
      北海道大学電子科学研究所(札幌市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion2012

    • Author(s)
      Tsukasa Oikawa, Masaaki Oyama, Hiroko Kozuka-Hata, Shunsuke Uehara, Nobuyuki Udagawa, Hideyuki Saya, Koichi Matsuo
    • Organizer
      ASBMR (American Society for Bone Mineral Research) 2012 Annual Meeting
    • Place of Presentation
      Minneapolis Convention Center(Minneapolis, USA)(ポスター発表)
    • Related Report
      2013 Final Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion2012

    • Author(s)
      Tsukasa Oikawa, Shunsuke Uehara, Nobuyuki Udagawa, Koichi Matsuo
    • Organizer
      第30回日本骨代謝学会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)(ポスター発表)
    • Related Report
      2013 Final Research Report
  • [Presentation] NFATc1 promotes cancer cell invasion via altered E-cadherin regulation2012

    • Author(s)
      Tsukasa Oikawa, Atsuko Nakamura, Koichi Matsuo, Hideyuki Saya
    • Organizer
      第64回日本細胞生物学会
    • Place of Presentation
      神戸国際会議場(神戸市)(ポスター発表)
    • Related Report
      2013 Final Research Report
  • [Presentation] NFATc1 promotes cancer cell invasion via altered E-cadherin regulation2012

    • Author(s)
      Tsukasa Oikawa, Atsuko Nakamura, Koichi Matsuo and Hideyuki Saya
    • Organizer
      第64回日本細胞生物学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion.2012

    • Author(s)
      Oikawa T, Oyama M, Kozuka-Hata H, Uehara S, Udagawa N, Saya H, Matsuo K.
    • Organizer
      ASBMR (American Society for Bone Mineral Research) 2012 Annual Meeting
    • Place of Presentation
      Minneapolis, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes mediates cell-cell fusion2011

    • Author(s)
      及川司
    • Organizer
      Bio-Rheumatology International Congress
    • Place of Presentation
      ヒルトン東京ベイホテル(東京)(招待ポスター発表)
    • Year and Date
      2011-11-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes mediates cell-cell fusion2011

    • Author(s)
      及川司
    • Organizer
      Podosomes, Invadopodia and Focal Adhesions in Physiology and Pathology
    • Place of Presentation
      Ayre Gran Hotel Colon(スペイン、マドリッド)
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes mediates cell-cell fusion2011

    • Author(s)
      及川司
    • Organizer
      第29回日本骨代謝学会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2011-07-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes mediates cell-cell fusion2011

    • Author(s)
      及川司
    • Organizer
      第63回日本細胞生物学会
    • Place of Presentation
      北海道大学(北海道)
    • Year and Date
      2011-06-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes mediates cell-cell fusion2011

    • Author(s)
      Tsukasa Oikawa, Masaaki Oyama, Hiroko Kozuka-Hata, Shunsuke Uehara, Nobuyuki Udagawa, Hideyuki Saya, Koichi Matsuo
    • Organizer
      Bio-Rheumatology International Congress
    • Place of Presentation
      Sheraton Grande Tokyo Bay Hotel(Urayasu, Japan)(ポスター発表)
    • Related Report
      2013 Final Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes mediates cell-cell fusion2011

    • Author(s)
      Tsukasa Oikawa, Masaaki Oyama, Hiroko Kozuka-Hata, Shunsuke Uehara, Nobuyuki Udagawa, Hideyuki Saya, Koichi Matsuo
    • Organizer
      Podosomes, Invadopodia and Focal Adhesions in Physiology and Pathology
    • Place of Presentation
      Ayre Gran Hotel Colon(Madrid, Spain)(ポスター発表)
    • Related Report
      2013 Final Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes mediates cell-cell fusion2011

    • Author(s)
      Tsukasa Oikawa, Masaaki Oyama, Hiroko Kozuka-Hata, Hideyuki Saya, Koichi Matsuo
    • Organizer
      第29回日本骨代謝学会
    • Place of Presentation
      大阪国際会議場(大阪市)(ポスター発表)
    • Related Report
      2013 Final Research Report
  • [Presentation] Tks5-dependent formation of circumferential podosomes mediates cell-cell fusion2011

    • Author(s)
      Tsukasa Oikawa, Masaaki Oyama, Hiroko Kozuka-Hata, Hideyuki Saya, Koichi Matsuo
    • Organizer
      第63回日本細胞生物学会
    • Place of Presentation
      北海道大学(札幌市)(ポスター発表)
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.careerpath-prj.keio.ac.jp/kanrinmaru/scholar/oikawa/

    • Related Report
      2013 Final Research Report
  • [Remarks] 慶應咸臨丸プロジェクトHP (及川司)

    • URL

      http://www.careerpath-prj.keio.ac.jp/kanrinmaru/scholar/oikawa/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 慶應咸臨丸プロジェクトHP (及川司)

    • URL

      http://www.careerpath-prj.keio.ac.jp/kanrinmaru/scholar/oikawa/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.careerpath-prj.keio.ac.jp/kanrinmaru/scholar/oikawa/

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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