The role of mDia, a Rho effector molecule, in tumorigenesis

• Project/Area Number: 22501011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kyoto University
• Principal Investigator: ISHIZAKI Toshimasa 京都大学, 大学院・医学研究科, 准教授 (70293876)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Rho / mDia / アクチン細胞骨格 / 細胞悪性化 / Ras / Src / CitronK / 遺伝子欠損マウス / 細胞内情報伝達 / 細胞移動 / 足場依存性増殖

Research Abstract

Although it has been reported that the small GTPase Rho is overexpressed in various clinical cancers, the role of Rho in tumorigenesis is still unknown. In this study, we dissected the contribution and function of mDia, a Rho effector molecule, in tumorigenesis. Furthermore, we analyzed physiological roles of Rho-mDia signaling and identified a novel regulatory mechanism of mDia-mediated actin polymerization. These studies are expected to elucidate the molecular mechanism and influence of Rho-mDia signaling in tumorigenesis.

Research Products

• [Journal Article] Citron-kinase mediates trasition from constriction to abscission through its coiled-coil domain (2013)
  • Author(s): Watanabe S, De Zan T, Ishizaki T, Narumiya S.
  • Journal Title: Journal of Cell Science Volume: (印刷中(in press) Pages: 1773-1784
  • DOI: 10.1242/jcs.116608
  • Peer Reviewed
• [Journal Article] A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors. (2012)
  • Author(s): Shinohara R, Thumkeo D, Kamijo H, Kaneko N, Sawamoto K, Watanabe K, Takebayashi H, Kiyonari H, Ishizaki T, Furuyashiki T, Narumiya S.
  • Journal Title: Nat Neurosci Volume: 15 Pages: 373-380
  • NAID: 120003726113
  • Peer Reviewed
• [Journal Article] Liprin-α controls stress fiber formation by binding to mDia and regulating its membrane localization (2012)
  • Author(s): Sakamoto S, Ishizaki T, Okawa K, Watanabe S, Arakawa T, Watanabe N, Narumiya S
  • Journal Title: Journal of Cell Science Volume: 125(1) Issue: 1 Pages: 108-120
  • DOI: 10.1242/jcs.087411
  • Peer Reviewed
• [Journal Article] A new role of multi scaffold protein Liprin-α: Liprin-α suppresses Rho-mDia mediated stress fiber formation (2012)
  • Author(s): Sakamoto S, Narumiya S, Ishizaki T
  • Journal Title: Bioarchitecture. Volume: 2 Pages: 43-49
  • Peer Reviewed
• [Journal Article] A new role of multi scaffold protein Liprin-α: Liprin-α suppresses Rho-mDia mediated stress fiber formation (2012)
  • Author(s): Sakamoto S et al
  • Journal Title: Bioarchitecture Volume: 2 Pages: 43-49
  • Peer Reviewed
• [Journal Article] A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors (2012)
  • Author(s): 篠原亮太
  • Journal Title: Nature Neuroscience Volume: 15 Issue: 3 Pages: 373-380
  • DOI: 10.1038/nn.3020
  • NAID: 120003726113
  • Peer Reviewed
• [Journal Article] Rotational movement of the formin mDia1 along the double helical strand of an actin filament. (2011)
  • Author(s): Mizuno H, Higashida C, Yuan Y, Ishizaki T, Narumiya S, Watanabe N.
  • Journal Title: Science. Volume: 331 Issue: 6013 Pages: 80-83
  • DOI: 10.1126/science.1197692
  • Peer Reviewed
• [Journal Article] Impaired vascular remodeling in the yolk sac of embryos deficient in ROCK-I and ROCK-II. (2011)
  • Author(s): Kamijo H, Matsumura Y, Thumkeo D, Koike S, Masu M, Shimizu Y, Ishizaki T, Narumiya S.
  • Journal Title: Genes Cells Volume: 16 Issue: 10 Pages: 1012-1021
  • DOI: 10.1111/j.1365-2443.2011.01546.x
  • Peer Reviewed
• [Journal Article] Deficiency of mDia, an Actin Nucleator, Disrupts Integrity of Neuroepithelium and Causes Periventricular Dysplasia (2011)
  • Author(s): タムケオ ディーン、篠原亮太
  • Journal Title: PLoS One Volume: 6 Issue: 9 Pages: e25465-e25465
  • DOI: 10.1371/journal.pone.0025465
  • Peer Reviewed
• [Journal Article] Impaired vascular remodeling in the yolk sac of embryos deficient in ROCK-I and ROCK-II (2011)
  • Author(s): Kamijo H, et al
  • Journal Title: Genes Cells Volume: 16 Pages: 1012-1021
  • Peer Reviewed
• [Journal Article] Rotational movement of mDial along the double helical strand of actin filament. (2011)
  • Author(s): Mizuno H., et al
  • Journal Title: Science Volume: 331 Pages: 80-83
  • Peer Reviewed
• [Journal Article] mDia1 targets v-Src to the cell periphery and facilitates cell transformation, tumorigenesis, and invasion (2010)
  • Author(s): Tanji M, Ishizaki T, Ebrahimi S, Tsuboguchi Y, Sukezane T, Akagi T, Frame MC, Hashimoto N, Miyamoto S, Narumiya S
  • Journal Title: Mol Cell Biol Volume: 30 Issue: 19 Pages: 4604-4615
  • DOI: 10.1128/mcb.00197-10
  • Peer Reviewed
• [Journal Article] Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells. (2010)
  • Author(s): Ohgushi M, Matsumura M, Eiraku M, Murakami K, Aramaki T, Nishiyama A, Muguruma K, Nakano T, Suga H, Ueno M, Ishizaki T, Suemori H, Narumiya S, Niwa H, Sasai Y
  • Journal Title: Cell Stem Cell Volume: 6 Issue: 2 Pages: 225-239
  • DOI: 10.1016/j.stem.2010.06.018
  • Peer Reviewed
• [Journal Article] Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells. (2010)
  • Author(s): Tanizaki H, Egawa G, Inaba K, Honda T, Nakajima S, Moniaga CS, Otsuka A, Ishizaki T, Tomura M, Watanabe T, Miyachi Y, Narumiya S, Okada T, Kabashima K
  • Journal Title: Blood. Volume: 116 Issue: 26 Pages: 5875-5884
  • DOI: 10.1182/blood-2010-01-264150
  • Peer Reviewed
• [Journal Article] Localization mechanisms of a Rho effector, mDia2, in cytokinesis. (2010)
  • Author(s): Watanabe S., et al
  • Journal Title: Molecular Biology of the Cell Volume: 21 Pages: 3193-3204
  • Peer Reviewed
• [Journal Article] mDial Targets v-Src to Cell Periphery and Facilitates Cell Transformation, Tumorigenesis and Invasion. (2010)
  • Author(s): Tanji, et al
  • Journal Title: Molecular and Cellular Biology Volume: 30 Pages: 4604-4615
  • Peer Reviewed
• [Journal Article] Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells (2010)
  • Author(s): Ohgushi M., et al
  • Journal Title: Cell Stem Cell Volume: 7 Pages: 225-239
  • Peer Reviewed
• [Journal Article] Rho-mDial pathway is required for adhesion, migration, and T cell stimulation in dendritic cells (2010)
  • Author(s): Tanizaki H., et al
  • Journal Title: Blood Volume: 116 Pages: 5875-5884
  • Peer Reviewed
• [Presentation] Roles of mDia2, an actin nucleator, in embryonic development. (2012)
  • Author(s): 石崎敏理
  • Organizer: 第35回 日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
  • Year and Date: 2012-12-14
• [Presentation] Liprin-a suppresses Rho-mDia mediated stress fiber formation (2012)
  • Author(s): 石崎敏理
  • Organizer: COLD SPRING HARBOR ASIA CONFERENCES Small GTPases at Different Scales: Proteins, Membranes, Cell.
  • Place of Presentation: Suzhou Dushu Lake Conference Center
  • Year and Date: 2012-09-28
• [Presentation] Roles of mDia2, an actin nucleator, in embryonic development (2012)
  • Author(s): 石崎敏理
  • Organizer: 第35回 日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
  • Invited
• [Presentation] Citron-kinase mediates transition from constriction to abscission through its coiled-coil domain (2012)
  • Author(s): 渡邉定則
  • Organizer: 第35回 日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
• [Presentation] 配偶子形成および受精におけるRho標的タンパク質mDiaの役割 (2012)
  • Author(s): 坂本智子
  • Organizer: 第59回日本実験動物学会総会
  • Place of Presentation: ビーコンプラザ（別府）
• [Presentation] Liprin-a suppresses Rho-mDia mediated stress fiber formation (2012)
  • Author(s): 石崎敏理
  • Organizer: COLD SPRING HARBOR ASIA CONFERENCES Small GTPases at Different Scales: Proteins, Membranes, Cell
  • Place of Presentation: Suzhou Dushu Lake Conference Center
  • Invited
• [Presentation] mDia, a Rho-regulated actin nucleator, is critical for tangential migration of cortical and olfactory inhibitory interneuron prtcursors (2012)
  • Author(s): Shinohara R., et al
  • Organizer: The 59th NIBB Conference
  • Place of Presentation: Okazaki Conterence Center Okazaki Japan
• [Presentation] Role of ROCK in embryogenesis (2011)
  • Author(s): Kamijo, H, et al
  • Organizer: 日本発生生物学会
  • Place of Presentation: 沖縄・沖縄コンベンションセンター
• [Presentation] Stabilization of the Midbody Structure by a Rho-effector, Citron (2011)
  • Author(s): Watanabe S, et al.
  • Organizer: 日本細胞生物学会
  • Place of Presentation: 札幌・北海道大学クラーク会館
• [Presentation] mDia, an actin nucleator and a Rho effector, is critical for tangential migration of cortical and olfactory bulb inhibitory interneuron (2011)
  • Author(s): Shinohara R., et al
  • Organizer: Gordon Research Conference : Mechanisms of Cell Signaling
  • Place of Presentation: Lewiston, ME, USA
• [Presentation] 神経前駆細胞の移動におけるRho標的分子mDiaの役割 (2011)
  • Author(s): Shinohara R., et al
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
• [Presentation] mDia, a Rho effector and act in nucleator, is critical for growth cone retraction in ephrin-induced axonal repulsion (2011)
  • Author(s): Toyoda Y, et al
  • Organizer: 日本生化学会
  • Place of Presentation: 京都・国立京都国際会館
• [Presentation] 神経前駆細胞の移動におけるRho標的分子mDiaの役割 (2011)
  • Author(s): Shinohara R., et al
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都・国立京都国際会館
• [Remarks]
  • URL: http://www5.mfour.med.kyoto-u.ac.jp/