Molecular Mechanism of Anchorage-Dependent and-Independent Proliferation

2010 Fiscal Year Final Research Report

• Project/Area Number: 18109003
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: The 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
• 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

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.

Research Products

• [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)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [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
• [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
• [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
• [Remarks] ホームページ
  • URL: http://www.cellcycle.m.u-tokyo.ac.jp/