Ror1-mediated signaling and its role in development and cancer

• Project/Area Number: 22790291
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: NISHITA Michiru 神戸大学, 大学院・医学研究科, 准教授 (30379359)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: Ror受容体チロシンキナーゼ / Wnt / がん / トリプルネガティブ乳癌 / Ror1 / Wnt5a / Ror / 受容体型チロシンキナーゼ

Research Abstract

Mouse embryonic fibroblasts isolated from Ror1 ; Ror2 double knockout mice and human Burkitt's lymphoma cells were used to study their responses to Wnt5a. We found that inhibition of Wnt/.-catenin signaling by Wnt5a is mediated not only by Ror2 but also by Ror1. We also found that Ror1 is overexpressed in human triple-negative breast cancer cells and thereby activates signaling molecules, such as c-Src, Akt, Erk and Stat3, and cell proliferation.

Research Products

• [Journal Article] Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis (2012)
  • Author(s): Maeda, K., Kobayashi, Y., Udagawa, N., Uehara, S., Ishihara, A., Mizoguchi, T., Kikuchi, Y., Takada, I., Kato, S., Kani, S., Nishita, M., Marumo, K., Martin, T. J., Minami, Y., and Takahashi, N.
  • Journal Title: Nat. Med Volume: 18 Pages: 405-412
  • Peer Reviewed
• [Journal Article] Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex (2012)
  • Author(s): Endo, M., Doi, R., Nishita, M., and Minami, Y.
  • Journal Title: J. Cell Sci
  • Peer Reviewed
• [Journal Article] Dissection of Wnt5a-Ror2 Signaling Leading to Matrix Metalloproteinase(MMP-13) Expression (2012)
  • Author(s): Yamagata, K., Li, X., Ikegaki, S., Oneyama, C., Okada, M., Nishita, M., and Minami, Y.
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 1588-1599
  • Peer Reviewed
• [Journal Article] Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis (2012)
  • Author(s): Maeda, K., Kobayashi, Y., Udagawa, N., Uehara, S., Ishihara, A., Mizoguchi, T., Kikuchi, Y., Takada, I., Kato, S., Kani, S., Nishita, M., Marumo, K., Martin, T.J., Minami, Y., Takahashi, N.
  • Journal Title: Nat.Med. Volume: (印刷中) Issue: 3 Pages: 405-12
  • DOI: 10.1038/nm.2653
  • Peer Reviewed
• [Journal Article] Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex (2012)
  • Author(s): Endo M, Doi R, Nishita M, Minami Y
  • Journal Title: Journal of Cell Science Volume: (印刷中)(掲載確定) Pages: 2017-2029
  • DOI: 10.1242/jcs.097782
  • Peer Reviewed
• [Journal Article] Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase(MMP-13) expression (2012)
  • Author(s): Yamagata K, Li X, Ikegaki S, Oneyama C, Okada M, Nishita M, Minami Y
  • Journal Title: J Biol Chem Volume: 287(2) Issue: 2 Pages: 1588-99
  • DOI: 10.1074/jbc.m111.315127
  • Peer Reviewed
• [Journal Article] Analysis of Wnt/planar cell polarity pathway in cultured cells (2012)
  • Author(s): 西田満
  • Journal Title: Methods in Molecular Biology Volume: 839 Pages: 201-214
  • DOI: 10.1007/978-1-61779-510-7_16
  • ISBN: 9781617795091, 9781617795107
• [Journal Article] Critical role of Wnt5a. Ror2 signaling in motility and invasiveness of carcinoma cells following Snail-mediated epithelial-mesenchymal transition (2011)
  • Author(s): Ren, D., * Minami, Y., and* Nishita, M.
  • Journal Title: Genes Cells Volume: 16 Pages: 304-315
  • Peer Reviewed
• [Journal Article] Critical role of Wnt5a-Ror2 signaling in motility and invasiveness of carcinoma cells following Snail-mediated epithelial-mesenchymal transition (2011)
  • Author(s): 西田満
  • Journal Title: Genes to Cells Volume: 16巻 Pages: 304-315
  • Peer Reviewed
• [Journal Article] Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization (2010)
  • Author(s): Nishita, M., Itsukushima, S., Nomachi, A., Endo, M., Wang, Z., Inaba, D., Qiao, S., Takada, S., Kikuchi, A., and* Minami, Y.
  • Journal Title: Mol. Cell. Biol Volume: 30 Pages: 3610-3619
  • Peer Reviewed
• [Journal Article] Cell/tissue-tropic functions of Wnt5a signaling in normal and cancer cells (2010)
  • Author(s): Nishita, M., Enomoto, M., Yamagata, K., and Minami, Y.
  • Journal Title: Trends Cell Biol Volume: 20 Pages: 346-354
  • Peer Reviewed
• [Journal Article] Cell/tissue-tropic functions of Wnt5a signaling in normal and cancer cells (2010)
  • Author(s): 西田満
  • Journal Title: Trends in Cell Biology Volume: 20巻 Pages: 346-354
  • Peer Reviewed
• [Journal Article] Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization (2010)
  • Author(s): 西田満
  • Journal Title: Molecular and Cellular Biology Volume: 30巻 Pages: 3610-3619
  • Peer Reviewed
• [Presentation] Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex (2011)
  • Author(s): 遠藤光晴
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学
  • Year and Date: 2011-06-28
• [Presentation] Wnt5a-Ror2シグナルによる細胞極性・移動制御とがんの浸潤 (2010)
  • Author(s): 南康博
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪国際会議場(大阪府)(招待講演)
  • Year and Date: 2010-05-20
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/medzoo/
• [Patent(Industrial Property Rights)] 疾患モデルとしての細胞種・組織特異的Ror2ノックアウトマウス (2011)
  • Inventor(s): 南康博、西田満、可児修一
  • Industrial Property Rights Holder: 神戸大学
  • Industrial Property Number: 2011-071014
  • Filing Date: 2011-03-28