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Mechanism for coordination of cell motility and proliferation in epithelial cells: role of intercellular mechanical interaction

Research Project

Project/Area Number 19K23748
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0702:Biology at cellular to organismal levels, and related fields
Research InstitutionNagoya University

Principal Investigator

Hirata Hiroaki  名古屋大学, 医学系研究科, 特任講師 (90414028)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsメカノバイオロジー / 細胞協同現象 / アドヘレンスジャンクション / 葉状仮足 / Rac1
Outline of Research at the Start

上皮組織が正常に形成され機能するためには、上皮細胞の運動と増殖の両者が適切に制御される必要がある。本研究では、稠密状態での上皮細胞において運動と増殖が協調的に制御されるメカニズムを解明する。稠密状態においては細胞どうしが物理的に接着していることから、細胞間の力のやり取りに特に着目し、仮足突出による細胞間押力およびアクトミオシン収縮による細胞間引張力が細胞運動と増殖の制御に果たす役割を明らかにする。

Outline of Final Research Achievements

Development and function of epithelial tissues depend on optimal regulations of motility and proliferation of epithelial cells. In this study, using cultured monolayers of epidermal cells, we examined the mechanism for coordinated regulation of cell motility and proliferation. We showed that Rac1, a master regulator of lamellipodia formation which drives collective cell migration, promoted both cell motility and cell cycle progression in epidermal monolayers. Disruption of the cell-cell adhesion structure, adherens junction (AJ), disturbed time-dependent coordination of cell motility and cell cycle progression after seeding cells, indicating a crucial role of AJ in coordinating motile and proliferative abilities in monolayered epidermal cells. These results were reported in iScience.

Academic Significance and Societal Importance of the Research Achievements

上皮組織の発生・機能・恒常性にとって上皮細胞の運動と増殖の両者が時空間的に協調して制御されることが必須であるものの、そのしくみは不明であった。本研究は、表皮多細胞系においてRac1が運動と増殖の共通の駆動因子であることを明らかにするとともに、アドヘレンスジャンクションを介した細胞間のコミュニケーションが運動と増殖を協調させるのに必要であることを解明した。これらの結果は、上皮組織という多細胞システムにおける動的挙動制御のメカニズムに重要な知見を与えるとともに、その破綻としてのがんにおける細胞の振る舞いを理解するのにも貢献するものと考えられる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report

Research Products

(9 results)

All 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (4 results) (of which Invited: 4 results)

  • [Journal Article] Coordination between Cell Motility and Cell Cycle Progression in Keratinocyte Sheets via Cell-Cell Adhesion and Rac12020

    • Author(s)
      Hirata Hiroaki、Dobrokhotov Oleg、Sokabe Masahiro
    • Journal Title

      iScience

      Volume: 23 Pages: 101729-101729

    • DOI

      10.1016/j.isci.2020.101729

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell mechanosensing underlies homeostasis of multicellular systems2020

    • Author(s)
      Nonomura Keiko、Hirata Hiroaki
    • Journal Title

      BIOPHYSICS

      Volume: 17 Issue: 0 Pages: 100-102

    • DOI

      10.2142/biophysico.bsj-2020019

      10.2142/biophysico.BSJ-2020019

    • NAID

      130007919803

    • ISSN
      2189-4779
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MMP24 as a Target of YAP Is a Potential Prognostic Factor in Cancer Patients2020

    • Author(s)
      Wataru Sugimoto、Katsuhiko Itoh、Hiroaki Hirata、Yoshinori Abe、Takeru Torii、Yasumasa Mitsui、Yemima Budirahardja、Nobuyuki Tanaka、Keiko Kawauchi
    • Journal Title

      Bioengineering

      Volume: 7 Pages: 18-18

    • DOI

      10.3390/bioengineering7010018

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tension-dependent Generation of Biochemical Signals on Actomyosin Fibers2020

    • Author(s)
      Hiroaki Hirata、Masahiro Sokabe
    • Journal Title

      Biophysics

      Volume: 60 Issue: 2 Pages: 089-093

    • DOI

      10.2142/biophys.60.089

    • NAID

      130007818289

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 細胞増殖の接触阻害における物理的因子の役割2020

    • Author(s)
      平田宏聡、Oleg Dobrokhotov、曽我部正博
    • Journal Title

      実験医学

      Volume: 38 Pages: 93-99

    • Related Report
      2019 Research-status Report
  • [Presentation] 角化細胞の増殖の接触阻害には接着結合の引張力が必須である2020

    • Author(s)
      平田宏聡、Oleg Dobrokhotov、曽我部正博
    • Organizer
      日本生物物理学会第58回年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 細胞外基質硬度による焦点接着斑―アクチン骨格系調節の分子・生物物理基盤2020

    • Author(s)
      平田宏聡
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Molecular and biophysical bases for modulation of the focal adhesion-actin cytoskeleton system in response to extracellular substrate rigidity2020

    • Author(s)
      平田宏聡
    • Organizer
      第53回生物機械システム研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] RhoA activation induces cell cycle exit and differentiation of skin cancer cells2019

    • Author(s)
      Oleg Dobrokhotov、Masahiro Sokabe、Hiroaki Hirata
    • Organizer
      日本生物物理学会第57回年会
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-09-03   Modified: 2022-01-27  

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