Roles of Wnt5a-Ror2 in actin dynamics and cell migration

• Project/Area Number: 19790233
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Kobe University
• Principal Investigator: NISHITA Michiru Kobe University, 大学院・医学研究科, 准教授 (30379359)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: Wnt5a / Ror2 / 細胞移動 / 細胞骨格 / 浸潤突起 / アクチン細胞骨格 / MMP-13 / アクチンコメット

Research Abstract

我々は受容体型チロシンキナーゼRor2がWnt5a受容体としてWnt5aによる細胞の極性化や細胞移動に必要であることを明らかにした。また、ヒト骨肉腫細胞株において、Wnt5aまたはRor2の発現を抑制した結果、浸潤能が顕著に低下した。さらに骨肉腫細胞においてRor2およびWnt5aによって遺伝子発現が制御される分子として、マトリックスメタロプロテアーゼMMP-13を同定し、MMP-13がWnt5a-Ror2シグナルによる骨肉腫細胞の浸潤に重要な役割を果たしていることが明らかになった。

Research Products

• [Journal Article] Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development (2008)
  • Author(s): He F., Xiong W., Yu X., Espinoza-Lewis R., Liu C., Gu S., Nishita M., Suzuki K., Yamada G., Minami Y., Chen Y.
  • Journal Title: Development 135 Pages: 3871-3879
  • Peer Reviewed
• [Journal Article] Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A (2008)
  • Author(s): Nomachi A., Nishita M., Inaba D., Enomoto M., Hamasaki M., Minami Y.
  • Journal Title: J. Biol. Chem. 283 Pages: 27973-27981
  • Peer Reviewed
• [Journal Article] Cthrcl selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex (2008)
  • Author(s): Yamamoto S., Nishimura O., Misaki K., Nishita M., Minami Y., Yonemura S., Tarui H., Sasaki H.
  • Journal Title: Dev. Cell 15 Pages: 23-36
  • Peer Reviewed
• [Journal Article] Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development (2008)
  • Author(s): Fenglei He
  • Journal Title: Development 135巻 Pages: 3871-3879
  • Peer Reviewed
• [Journal Article] Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A (2008)
  • Author(s): 野町昭
  • Journal Title: Journal of Biological Chemistry 283巻 Pages: 27973-27981
  • Peer Reviewed
• [Journal Article] Cthrcl selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex (2008)
  • Author(s): 山元進司
  • Journal Title: Developmental Cell 15巻 Pages: 23-36
  • Peer Reviewed
• [Journal Article] Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2 (2008)
  • Author(s): Changgong Li
  • Journal Title: BMC Molecular Biology 9巻
  • Peer Reviewed
• [Journal Article] Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2. (2007)
  • Author(s): 山本 裕之
  • Journal Title: Genes to Cells 12巻11号 Pages: 1215-1223
  • Peer Reviewed
• [Journal Article] Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling
  • Author(s): Enomoto M., Hayakawa S., Itsukushima S., Ren D., Matsuo M., Tamada K., Oneyama C., Okada M., Takumi T., Nishita M., Minami Y.
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] Ror-family receptor tyrosine kinases in non-canonical Wnt signaling : Their implications in developmental morphogenesis and human diseases
  • Author(s): Minami Y., Oishi I., Endo M., Nishita M.
  • Journal Title: Dev. Dyn. (In press)
  • Peer Reviewed
• [Presentation] Wnt5a/Ror2シグナルによる細胞運動制御 (2008)
  • Author(s): 西田 満
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Wnt5a/Ror2シグナルによる細胞運動制御 (2008)
  • Author(s): 西田満
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Regulation of Dishevelled in Wnt5a/Ror2 signaling (2008)
  • Author(s): 西田 満
  • Organizer: 第2回日韓共同研究プログラム合同ミーティング
  • Place of Presentation: 広島
  • Year and Date: 2008-11-21
• [Presentation] Regulation of Dishevelled in Wnt5a/Ror2 signaling (2008)
  • Author(s): 西田満
  • Organizer: 日韓共同研究プログラム第2回二国間会議
  • Place of Presentation: 広島
  • Year and Date: 2008-11-21
• [Presentation] Ror2 regulates cytoskeletal rearrangements to mediate Wnt5a-induced polarized cell migration (2007)
  • Author(s): 西田満
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] Ror2 regulates cytoskeletal rearrangements to mediate Wnt5a-induced polarized cell migration (2007)
  • Author(s): 西田 満
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] Role of Ror2 receptor tyrosine kinase in the regulation of Wnt5a-induced cell polarization and migration (2007)
  • Author(s): 西田 満
  • Organizer: 第1回日韓共同研究プログラム合同ミーティング
  • Place of Presentation: 韓国
  • Year and Date: 2007-10-26