Protein tyrosine phosphatases and regulation of cancer cell adhesion/migration

2009 Fiscal Year Final Research Report

• Project/Area Number: 17014010
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Gunma University
• Principal Investigator: MATOZAKI Takashi Gunma University, 生体調節研究所, 教授 (80252782)
• Co-Investigator(Kenkyū-buntansha): OHNISHI Hiroshi 群馬大学, 生体調節研究所, 准教授 (70334125) ; OKAZAWA Hideki 群馬大学, 生体調節研究所, 助教 (80334126) ; MURATA Yoji 群馬大学, 生体調節研究所, 助教 (60400735)
• Project Period (FY): 2005 – 2009
• Keywords: 癌 / 酵素 / シグナル伝達 / 生体分子

Research Abstract

In this grant project, we have investigated the physiological role of protein tyrosine phosphorylation as well as its relation to oncogenesis and metastasis. We have clarified that a novel cell-cell communication system “CD47-SHPS-1 system" or SAP-1, a receptor-type protein tyrosine phosphatase, is important for regulation of cancer metastasis and of inflammation that is directly related to development of cancers.

Research Products

• [Journal Article] Promotion of cell spreading and migration by vascular endothelial-protein tyrosine phosphatase (VE-PTP) in cooperation with integrins. (2010)
  • Author(s): Mori, M., Murata, Y., Kotani, T., Kusakari, S., Ohnishi, H., Saito, Y., Okazawa, H., Ishizuka, T., Mori, M., Matozaki, T.
  • Journal Title: J. Cell. Physiol. 224 Pages: 195-204
  • Peer Reviewed
• [Journal Article] Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine phosphatases and their complex formations with Grb2 or Fyn. (2010)
  • Author(s): Murata, Y., Mori, M., Kotani, T., Supriatna, Y., Okazawa, H., Kusakari, S., Saito, Y., Ohnishi, H., Matozaki, T.
  • Journal Title: Genes Cells 15 Pages: 513-524
  • Peer Reviewed
• [Journal Article] Functions and molecular mechanisms of the CD47-SIRPα signalling pathway. (2009)
  • Author(s): Matozaki, T., Murata, Y., Okazawa, H., Ohnishi, H.
  • Journal Title: Trends Cell Biol. 19 Pages: 72-80
  • Peer Reviewed
• [Journal Article] SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis. (2009)
  • Author(s): Sadakata, H., Okazawa, H., Sato, T., Supriatna, Y., Ohnishi, H., Kusakari, S., Murata, Y., Ito, T., Nishiyama, U., Minegishi, T., Harada, A., Matozaki, T.
  • Journal Title: Genes Cells 14 Pages: 295-308
  • Peer Reviewed
• [Journal Article] Protein tyrosine phosphatase SHP-2: A proto-oncogene product that promotes Ras activation. (2009)
  • Author(s): Matozaki, T., Murata, Y., Saito, Y., Okazawa, H., Ohnishi, H.
  • Journal Title: Cancer Sci. 100 Pages: 1786-1793
  • Peer Reviewed
• [Journal Article] Inhibitory regulation of osteoclast bone resorption by signal regulatory protein (2009)
  • Author(s): van Beek, E.M., de Vries, T.J., Mulder, L., Schoenmaker, T., Hoeben, K.A., Matozaki, T., Langenbach, G.E.J., Kraal, G., Everts, V., van den Berg, T.K.
  • Journal Title: FASEB J. 23 Pages: 4081-4090
  • Peer Reviewed
• [Journal Article] Signal regulatory protein-β1: a microglial modulator of phagocytosis in Alzheimer's disease. (2009)
  • Author(s): Gaikwad, S., Larionov, Wang, Y., Dannenberg, H., Matozaki, T., Monsonego, A., Thal, D.R., Neumann, H.
  • Journal Title: Am. J. Pathol. 175 Pages: 2528-2539
  • Peer Reviewed
• [Journal Article] Trans-endocytosis of CD47 and SHPS-1 and its role in regulation of the CD47-SHPS-1 system. (2008)
  • Author(s): Kusakari, S., Ohnishi, H., Jin, F. -J., Kaneko, Y., Murata, T., Murata, Y., Okazawa, H., Matozaki, T.
  • Journal Title: J. Cell Sci. 121 Pages: 1213-1223
  • Peer Reviewed
• [Journal Article] Negative regulation by SHPS-1 of Toll-like receptor-dependent proinflammatory cytokine production in macrophages. (2008)
  • Author(s): Miyake, A., Murata, Y., Okazawa, H., Ikeda, H., Niwayama, Y., Ohnishi, H., Hirata, Y., Matozaki, T.
  • Journal Title: Genes Cells 3 Pages: 209-219
  • Peer Reviewed
• [Journal Article] Essential roles of SHPS-1 in induction of contact hypersensitivity of skin. (2008)
  • Author(s): Motegi, S., Okazawa, H., Murata, Y., Kanazawa, Y., Saito, Y., Kobayashi, H., Ohnishi, H., Oldenborg, P. -A., Ishikawa, O., Matozaki, T.
  • Journal Title: Immunol. Lett. 121 Pages: 52-60
  • Peer Reviewed
• [Journal Article] Structural insight into the specific interaction between murine SHPS-1/SIRPα and its ligand CD47. (2008)
  • Author(s): Nakaishi, A., Hirose, M., Yoshimura, M., Oneyama, C., Saito, K., Kuki, N., Matsuda, M., Honma, N., Ohnishi, H., Matozaki, T., Okada, M., Nakagawa, A.
  • Journal Title: J. Mol. Biol. 375 Pages: 650-660
  • Peer Reviewed
• [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages. (2008)
  • Author(s): Kuroda, S., Nishio, M., Sasaki, T., Horie, Y., Kawahara, K., Sasaki, M., Natsui, M., Matozaki, T., Tezuka, H., Ohteki, T., Forster, I., Mak, T.W., Nakano, T., Suzuki A.
  • Journal Title: Eur. J. Immunol. 38 Pages: 1331-1340
  • Peer Reviewed
• [Journal Article] Resistance to experimental autoimmune encephalomyelitis and impaired T cell priming by dendritic cells in SHPS-1 mutant mice. (2007)
  • Author(s): Tomizawa, T., Kaneko, Y., Kaneko, Y., Saito, Y., Ohnishi, H., Okajo, J., Okuzawa, C., Ishikawa-Sekigami, T., Murata, Y., Okazawa, H., Okamoto, K., Nojima, Y. Matozaki, T.
  • Journal Title: J. Immunol. 179 Pages: 869-877
  • Peer Reviewed
• [Journal Article] Regulation by Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 of α-galactosylceramide-induced antimetastatic activity and Th1 and Th2 responses of NKT cells. (2007)
  • Author(s): Okajo, J., Kaneko, Y., Murata, Y., Tomizawa, T., Okuzawa, C., Saito, Y., Kaneko, Y., Ishikawa-Sekigami, T., Okazawa, H., Ohnishi, H., Matozaki, T. Nojima, Y.
  • Journal Title: J. Immunol. 178 Pages: 6164-6172
  • Peer Reviewed
• [Journal Article] SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages. (2006)
  • Author(s): Ishikawa-Sekigami, T., Kaneko, Y., Okazawa, H., Tomizawa, T., Okajo, J., Saito, Y., Okuzawa, C., Sugawara-Yokoo, M., Nishiyama, U., Ohnishi, H., Matozaki, T. Nojima, Y.
  • Journal Title: Blood 107 Pages: 341-348
  • Peer Reviewed
• [Journal Article] Mutational analysis of the mechanism of negative regulation by SHPS-1 of phagocytosis in macrophages. (2006)
  • Author(s): Ikeda, H., Okazawa, H., Ohnishi, H., Murata, Y., Oldenborg, P. -A. Matozaki, T.
  • Journal Title: J. Immunol. 177 Pages: 3123-3132
  • Peer Reviewed
• [Journal Article] CD47 regulation of epithelial cell spreading and migration, and its signal transduction. (2006)
  • Author(s): Shinohara, M., Ohyama, N., Murata, Y., Okazawa, H., Ohnishi, H., Ishikawa, O., Matozaki, T.
  • Journal Title: Cancer Sci. 97 Pages: 889-895
  • Peer Reviewed
• [Journal Article] Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system. (2005)
  • Author(s): Okazawa, H., Motegi, S., Ohyama, N., Ohnishi, H., Tomizawa, T., Kaneko, Y., Oldenborg, P. -A., Ishikawa, O., Matozaki, T.
  • Journal Title: J. Immunol. 174 Pages: 2004-2011
  • Peer Reviewed
• [Presentation] Tyrosine phosphorylation of SAP-1, a receptor-type protein tyrosine phosphatase, and its association with Grb2. (2009)
  • Author(s): Murata, Y., Kotani, Supriatna, Y., Mori, M., Okazawa, H., Ohnishi, H., Saito, Y., Matozaki, T.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-01
• [Presentation] Promotion by VE-PTP of lamellipodium formation in cooperation with Ras and integrin. (2009)
  • Author(s): M ori, M., Murata, Y., Ohnishi, H., Okazawa, H., Kotani, T., Saito, Y., Mori, M. Matozaki, T.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-01
• [Presentation] クラス3受容体型チロシンホスファターゼの機能と病態への関与 (2008)
  • Author(s): Y ana Supriatna、岡澤秀樹、村田陽二、大西浩史、的崎尚
  • 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: 神戸国際会議場(兵庫県)
  • Year and Date: 2008-12-09
• [Presentation] チロシンホスファターゼによるがん、炎症性腸炎の制御 (2008)
  • Author(s): 的崎尚、岡澤秀樹、村田陽二、大西浩史
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2008-10-28
• [Presentation] 細胞間シグナル伝達システムCD47-SHPS-1系とがんの浸潤・転移の制御, シンポジウム<浸潤・転移・血管新生研究の進歩> (2008)
  • Author(s): 的崎尚
  • Organizer: 第64回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2008-09-14
• [Presentation] SAP-1 is a microvillus-specific protein tyrosine phosphatase that regulates intestinal tumorigenesis. (2008)
  • Author(s): S adakata, H., Okazawa, H., Supriatna, Y., Ohnishi, H., Murata, Y., Matozaki, T.
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Snowmass, Colorado(USA)
  • Year and Date: 2008-07-13
• [Presentation] Regulation by CD47-SHPS-1 system of neurite development. (2007)
  • Author(s): M urata, T., Ohnishi, H., Kusakari, S., Murata, Y., Okazawa, H., Furuya, N., Matozaki, T.
  • Organizer: Neurosciense 2007
  • Place of Presentation: San Diego Convention center(サンディエゴ)
  • Year and Date: 2007-11-03
• [Presentation] SHPS-1による皮膚免疫とToll様受容体を介したサイトカイン産生の制御 (2007)
  • Author(s): 茂木精一郎、岡澤秀樹、小林久江、村田陽二、大西浩史、石川治、的崎尚
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2007-10-03
• [Presentation] Trans-endocytosis of CD47-SHPS-1 system and its molecular mechanism. (2007)
  • Author(s): K usakari, S., Ohnishi, H., Okazawa, H., Murata, T., Murata, Y., Matozaki, T.
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2007-10-03
• [Presentation] NKT細胞の活性化と癌転移抑制におけるSHPS-1の役割 (2006)
  • Author(s): 岡上準、金子和光、村田陽二、岡澤秀樹、大西浩史、野島美久、的崎尚, 他
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2006-09-28
• [Presentation] CD47 promotes neuronal development through Src-and FRG/Vav2-mediated activation of Rac and Cdc42. (2006)
  • Author(s): M urata, T., Ohnishi, H., Okazawa, H., Murata, Y., Kusakari, S., Hayashi, Y., Miyashita, M., Furuya, N., Matozaki, T.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2006-06-18
• [Presentation] A Novel Intercellular Communication System, The CD47-SHPS-1 System, in Neuronal Network. (2005)
  • Author(s): Ohnishi, H., Miyashita, M., Murata, T., Kaneko, Y., Okazawa, H., Matozaki, T.
  • Organizer: ISN-ESN:20th Biennial Meeting International Society for Neurochemistry jointly with the European Society for Neurochemistry
  • Place of Presentation: Congress Innsbruck(Innsbruck, Austria)
  • Year and Date: 2005-08-25
• [Book] シグナル伝達研究 (2009)
  • Author(s): 的崎尚、岡田雅人, 他
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.imcr.gunma-u.ac.jp/lab/biosig/
• [Patent(Industrial Property Rights)] マクロファージ活性化剤並びにその製造方法及びスクリーニング方法 (2008)
  • Inventor(s): 的崎尚、大西浩史
  • Industrial Property Rights Holder: 国立大学法人群馬大学
  • Industrial Property Number: 特許・第4224586号
  • Filing Date: 2008-12-05
  • Acquisition Date: 2008-12-05
• [Patent(Industrial Property Rights)] Pharmaceutical Composition and Method for Activating Macrophage Using the Same(医薬組成物及びそれを用いたマクロファージの活性化方法) (2008)
  • Inventor(s): 的崎尚、大西浩史
  • Industrial Property Rights Holder: 国立大学法人群馬大学
  • Industrial Property Number: 米国特許・第7, 449, 301号
  • Filing Date: 2008-11-11
  • Acquisition Date: 2008-11-11