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

2012 Fiscal Year Final Research Report

• 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
• Keywords: Rho / mDia / アクチン細胞骨格 / 細胞悪性化 / Ras / Src

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] 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
  • 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: J Cell Sci Volume: 125 Pages: 108-120
  • DOI: 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] 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 Pages: 80-83
  • DOI: 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 Pages: 1012-1021
  • DOI: 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): Thumkeo D, Shinohara R, Watanabe K, Takebayashi H, Toyoda Y, Tohyama K, Ishizaki T, Furuyashiki T, Narumiya S
  • Journal Title: PLoS One Volume: 6 Pages: e25465.
  • DOI: doi:10.1371/journal.pone.0025465
  • 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 Pages: 4604-4615
  • DOI: 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 Pages: 225-239
  • DOI: 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 Pages: 5875-5884
  • DOI: doi:10.1182/blood-2010-01-264150
  • Peer Reviewed
• [Journal Article] Citron kinase mediates transition from constriction to abscission through its coiled-coil domain.
  • Author(s): Watanabe S, De Zan T, Ishizaki T, Narumiya S.
  • Journal Title: J Cell Sci Volume: (in press)
  • DOI: doi:10.1242/jcs.116608
  • 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
• [Remarks]
  • URL: http://www5.mfour.med.kyoto-u.ac.jp/