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Molecular Mechanism of Anchorage-Dependent and-Independent Proliferation

Research Project

Project/Area Number 18109003
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

OKAYAMA Hiroto  The University of Tokyo, 大学院・医学系研究科, 教授 (40111950)

Project Period (FY) 2006 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥112,710,000 (Direct Cost: ¥86,700,000、Indirect Cost: ¥26,010,000)
Fiscal Year 2010: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2009: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2008: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2007: ¥30,810,000 (Direct Cost: ¥23,700,000、Indirect Cost: ¥7,110,000)
Fiscal Year 2006: ¥32,370,000 (Direct Cost: ¥24,900,000、Indirect Cost: ¥7,470,000)
Keywords癌 / 細胞周期 / シグナル伝達 / タンパク分解 / チェックポイント / mTORC1 / 足場 / 細胞間マトリックスタンパク / Cdc6 / APC / C^<Cdh1> / 発生分化 / 足場依存性増殖 / G1-S遷移制御 / ユビキチンリガーゼ / マウス胎性線維芽細胞 / Cdk6 / サイクリンD3
Research Abstract

Virtually all the cells composing solid organs of adult animals require an anchorage to the extracellular matrix and without this, arrest in G1 phase and die of apoptosis. Upon malignant transformation, these cells acquire the ability to proliferate without anchorage. This ability is generally believed to underlie their tumorigenicity. In this research project, we sought to understand the molecular mechanism controlling anchorage-dependent and-independent proliferation, which remains totally unknown, and now, the entire mechanism is largely understood. Consequently, a new, seemingly most effective target for anticancer therapy emerged.

Report

(7 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report   Self-evaluation Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (28 results)

All 2011 2010 2008 2007 2006 Other

All Journal Article (19 results) (of which Peer Reviewed: 16 results) Presentation (6 results) Remarks (3 results)

  • [Journal Article] Rho-associated Kinase Connects a Cell Cycle-controlling Anchorage Signal to the Mammalian Target of Rapamycin Pathway.2011

    • Author(s)
      Park, J.-H., Arakawa-Takeuchi, S., Jinno, S., Okayama, H.
    • Journal Title

      J.Biol.Chem. 掲載確定(印刷中)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mammalian Target of Rapamycin Complex 1 Signaling Opposes the Effects of Anchorage Loss, Leading to Activation of Cdk4 and Cdc6 Stabilization.2010

    • Author(s)
      Arakawa-Takeuchi, S., Kobayashi, K., Park, J.-H., Uranbileg, B., Yamamoto, H., Jinno, S., Okayama, H.
    • Journal Title

      FEBS Lett. 584

      Pages: 2779-2785

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mammalian target of rapamycin complex 1 signaling opposes the effects of anchorage loss, leading to activation of Cdk4 and Cdc6 stabilization.2010

    • Author(s)
      Arakawa-Takeuchi S., Kobayashi.K, Park JH, Uranbileg B, Yamamoto H, Jinno S, Okayama H.
    • Journal Title

      FEBS Lett.

      Volume: 584(13) Pages: 2779-2785

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cdc6 Determines Utilization of p21WAF1/CIP1-dependent Damage Checkpoint in S Phase Cells.2008

    • Author(s)
      Kan, Q., Jinno, S., Kobayashi, K., Yamamoto, H., Okayama, H.
    • Journal Title

      J.Biol.Chem. 283

      Pages: 17864-17872

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ATP-dependent activation of p21WAF1/CIP1-associated Cdk2 by Cdc6.2008

    • Author(s)
      Kan, Q., Jinno, S., Yamamoto, H., Kobayashi, K., Okayama, H.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 105

      Pages: 4757-4762

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cdc6 Determines Utilization of p21^<WAF1/CIP1>-dependent Damage Checkpoint in S Phase Cells2008

    • Author(s)
      Kan, Q., Jinno, S., Kobayashi, K., Yamamoto, H., and Okayama, H.
    • Journal Title

      J. Biol. Chem. 283

      Pages: 17864-17872

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] ATP-dependent activation of p21^<WAF1/CIP1>-associated Cdk2 by Cdc62008

    • Author(s)
      Kan,Q., Jinno, S., Yamamoto, H., Kobayashi, K., and Okayama, H.
    • Journal Title

      2008, Proc. Natl.Acad. Sci. USA. 105

      Pages: 4757-4762

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Cdc6 Determines Utilization ofp2l^<WAF1/C1P1>-dependent Damage Checkpoint in S Phase Cells.2008

    • Author(s)
      quiming Kan
    • Journal Title

      J. Biol. Chem. 283

      Pages: 17864-17872

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ATP-dependent activation of p21^WAF1/CIP1-associated Cdk2 by Cdc62008

    • Author(s)
      Qiuming Kan
    • Journal Title

      Proc.Natl.Acad.Sco.USA 105

      Pages: 4757-4762

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemical DNA damage activates p21^<WAF1/CIP1>-dependent intra-S checkpoint.2007

    • Author(s)
      Kan, Q., Jinno, S., Yamamoto, H., Okayama, H.
    • Journal Title

      FEBS Lett. 30

      Pages: 5879-5884

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemical DNA damage activates p21^<WAF1/CIP1>-dependent intra-S checkpoint2007

    • Author(s)
      Kan, Q., Jinno, S., Yamamoto, H., and Okayama, H.
    • Journal Title

      FEBS Lett. 30

      Pages: 5879-5884

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Chemical DNA damage activates p21^WAF1/CIP1-dependent intra-S checkpoint2007

    • Author(s)
      Qiuming Kan
    • Journal Title

      FEBS Lett 30

      Pages: 5879-5884

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wilms' tumor 1-associating protein regulates G2_M transition through stabilization of cyclin A2 mRNA.2006

    • Author(s)
      Horiuchi, K., Umetani, M., Minami, T., Okayama, H., Takada, S., Yamamoto, M., Aburatani, H., Reid, P.C., Housman, D.E., Hamakubo, T., Kodama, T.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 103

      Pages: 17278-17283

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gene delivery by aminofullerenes : Structure requirement for efficient transfection.2006

    • Author(s)
      Isobe, H., Nakanishi, W., Tomita, N., Jinno, S., Okayama, H., Nakamura, E.
    • Journal Title

      Chemistry an Asian Journal 1

      Pages: 168-175

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nonviral gene delivery by aminofullerene.2006

    • Author(s)
      Isobe, H., Nakanishi, W., Tomita, N., Jinno S., Okayama, H., Nakamura, E.
    • Journal Title

      Mol Pharm 3 3

      Pages: 124-134

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Wilms tumor 1-associating protein regulates G2_M transition through stabilization of cyclin A2 mRNA2006

    • Author(s)
      Horiuchi, K., Umetani, M., Minami, T., Okayama, H., Takada, S., Yamamoto, M., Aburatani, H., Reid, P. C., Housman, D. E., Hamakubo, T., and Kodama, T.
    • Journal Title

      Acad. Sci. USA 103

      Pages: 17278-17283

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Gene Delivery By Aminofullerenes : Structural Requirements forEfficient Trsnsfection.2006

    • Author(s)
      Isobe, H., Nakanishi, W., Tomita, N., Jinno, S., Okayama, H., Nakamura, E.
    • Journal Title

      Chem. Asian. J. 1-2

      Pages: 167-175

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nonviral gene delivery by tetraamino fullerene.2006

    • Author(s)
      Isobe, H., Nakanishi, W., Tomita, N., Jinno, S., Okayama, H., Nakamura, E.
    • Journal Title

      Mol. Pharm. 3 (2)

      Pages: 124-134

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Wilms' tumor 1-associating protein regulates G_2/M transition through stabilization of cyclin A2 mRNA.2006

    • Author(s)
      Horiuchi, K., Umetani, M., Minami, T., Okayami, H., Takeda, S., Yamamoto, M., Aburatani, H., Reid, PC., Housman DE., Hamakubo, T., Kodama, T.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. 103 (46)

      Pages: 17278-17283

    • Related Report
      2006 Annual Research Report
  • [Presentation] Mammalian target of rapamycin complex 1 signaling opposes the effects of anchorage loss, leading to activation of Cdk4 and Cdc6 stabilization.2010

    • Author(s)
      Arakawa-Takeuchi, S.
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸ポートピアホテル、神戸国際会議場、神戸国際展示場)(兵庫県神戸市)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Final Research Report
  • [Presentation] Efficient Induction of Anchorage-Independent Proliferation of Rat Embryonic Fibroblast by Overexpression of Cdk6,Cyclin D3,Cdc6 and aRhb.2010

    • Author(s)
      Uranbileg,B.
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸ポートピアホテル、神戸国際会議場、神戸国際展示場)(兵庫県神戸市)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Final Research Report
  • [Presentation] Rho-Associated Kinase Connects an Anchorage Signal to The Mammalian Target of Rapamycin.2010

    • Author(s)
      Park,J-H.
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸ポートピアホテル、神戸国際会議場、神戸国際展示場)(兵庫県神戸市)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Final Research Report
  • [Presentation] 足場シグナルはTSC2-Rheb-mTORC1経路を介してCdk4活性やCdc6の安定性を維持する/Mammalian target of rapamycin complex 1 signaling opposes the effects ofanchorage loss, leading to activation of Cdk4 and Cdc6 stabilization.2010

    • Author(s)
      竹内(荒川)志穂
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸ポートビアホテル,神戸国際会議場,神戸国際展示場)(兵庫県神戸市)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Efficient Induction of Anchorage-lndependent Proliferation of Rat Embryonic Fibroblast by Overexpression of Cdk6, Cyclin D3, Cdc6 and aRheb.2010

    • Author(s)
      Uranbileg Baasanjav
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸ポートビアホテル,神戸国際会議場,神戸国際展示場)(兵庫県神戸市)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Rho-Associated Kinase Connects an Anchorage Signal to the Mammalian Target of Rapamycin2010

    • Author(s)
      Jung-ha Park
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸ポートビァホテル,神戸国際会議場,神戸国際展示場)(兵庫県神戸市)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://www.cellcycle.m.u-tokyo.ac.jp/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.cellcycle.m.u-tokyo.ac.jp/

    • Related Report
      2008 Self-evaluation Report
  • [Remarks]

    • URL

      http://www.cellcycle.m.u-tokyo.ac.jp/

    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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