Functional analysis of RacGAP FilGAP in tumor invasion and metastasis

• Project/Area Number: 22700885
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Tumor biology
• Research Institution: Kitasato University
• Principal Investigator: SAITO KOJI 北里大学, 理学部, 助教 (70556901)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 細胞運動 / 細胞接着 / 細胞骨格 / 低分子量GTP結合蛋白質 / 浸潤、転移 / 癌 / シグナル伝達 / 低分子量Gタンパク / RacGAP / FilGAP

Research Abstract

FilGAP is a small GTPase Rac-specific GTPase-activating protein. I have studied the role of FilGAP in tumor invasion and metastasis. (1) FilGAP is required for mesenchymal-to-amoeboid transition in carcinoma cells. (2) Inactivation of Rac by FilGAP induces amoeboid migration. (3) Phosphorylation of FilGAP by ROCK mediates RhoA/ROCK-induced amoeboid migration. (4) FilGAP appears to mediate carcinoma cell invasion and metastasis. Thus, phosphorylation of FilGAP by ROCK promotes amoeboid migration of carcinoma cells, and FilGAP contributes to tumor invasion and metastasis.

Research Products

• [Journal Article] ADP Ribosylation Factor 6 (Arf6) Acts through FilGAP Protein to Down-regulate Rac Protein and Regulates Plasma Membrane Blebbing (2014)
  • Author(s): Kaori Kawaguchi, Koji Saito, Hisayo Asami, Yasutaka Ohta
  • Journal Title: THE JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 289 Pages: 9675-9682
  • Peer Reviewed
• [Journal Article] FilGAP, a Rho/Rho-associated protein kinase-regulated GTPase-activating protein for Rac, controls tumor cell migration (2012)
  • Author(s): Saito, K., Ozawa, Y., Hibino, K., Ohta, Y.
  • Journal Title: Mol. Biol. Cell Volume: vol.23 Pages: 4739-4750
  • Peer Reviewed
• [Journal Article] FilGAP, a Rho/Rho-associated protein kinase-regulated GTPase-activating protein for Rac, controls tumor cell migration (2012)
  • Author(s): Koji Saito
  • Journal Title: Molecular Biology of the Cell Volume: 23 Pages: 4739-4750
  • Peer Reviewed
• [Presentation] RacGAP 因子FilGAP は癌細胞の運動を制御する (2014)
  • Author(s): 斉藤康二
  • Organizer: 平成25年度がん研究分野の特性等を踏まえた支援活動公開シンポジウム
  • Place of Presentation: 一橋講堂学術総合センター(東京)
  • Year and Date: 2014-01-31
• [Presentation] a Rho/ROCK-regulated GAP for Rac controls tumor cell migration (2012)
  • Author(s): Saito, K.
  • Organizer: アメリカ細胞生物学会年会
  • Place of Presentation: Moscone Center (サンフランシスコ)
  • Year and Date: 2012-12-17
• [Presentation] RacGAP 因子FilGAP はRhoA/ROCK 経路を通じて癌細胞の形態変化を制御する (2011)
  • Author(s): 斉藤康二
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-16
• [Presentation] FilGAP regulates tumor cell morphology through RhoA/ROCK pathway (2011)
  • Author(s): 斉藤康二
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-16
• [Presentation] Arf6はRacGAP因子FilGAPを細胞膜へ移行してRacを不活化する
  • Author(s): 川口香織, 斉藤康二, 阿佐見久代, 太田安隆
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド 神戸国際展示場（兵庫県神戸市）
• [Presentation] FilGAP, a Rho/ROCK-regulated GAP for Rac controls tumor cell migration
  • Author(s): Koji Saito
  • Organizer: アメリカ細胞生物学会
  • Place of Presentation: Moscone Center (サンフランシスコ, アメリカ)
• [Remarks]
  • URL: http://www.kitasato-u.ac.jp/sci/resea/seibutsu/kino/Home.html