Disorganization of cell and tissue systems in cancer

2009 Fiscal Year Final Research Report

• Project/Area Number: 16060101
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kobe University (2008-2009); Osaka University (2004-2007)
• Principal Investigator: TAKAI Yoshimi Kobe University, 大学院・医学研究科, 教授 (60093514)
• Co-Investigator(Renkei-kenkyūsha): AKIYAMA Tetsu 東京大学, 分子細胞生物学研究所, 教授 (70150745) ; OHNO Shigeo 横浜市立大学, 大学院・医学研究科, 教授 (10142027) ; TSUKITA Shoichiro 京都大学, 大学院・医学研究科, 教授 (50155347) ; TAKENAWA Tadaomi 神戸大学, 大学院・医学研究科, 教授 (40101315) ; SEIKI Motoharu 東京大学, 医科学研究所, 教授 (10154634) ; TAKAKURA Nobuyuki 大阪大学, 微生物病研究所, 教授 (80291954)
• Project Period (FY): 2004 – 2009
• Keywords: がん / 細胞運動 / 細胞増殖 / 細胞接着 / 組織

Research Abstract

A number of previous studies revealed the properties of cancer cells at the levels of genes and cells, contributing to the elucidation of the mechanisms by which cancer is a life-threatening disease. Based on accumulating lines of evidence concerning cancer cells, it was systematically investigated in this project how "the initiation and progression of cancer" are induced in terms of the disorganization of cell and tissue systems in cancer. It was found that abnormalities of cell movement, proliferation, and adhesion in cancer cells play important roles in this disorganization.

Research Products

• [Journal Article] PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties. (2010)
  • Author(s): Nagahama Y, Ueno M, Miyamoto S, Morii E, Minami T, Mochizuki N, Saya H, Takakura N.
  • Journal Title: Cancer Res. 70(3) Pages: 1215-1224
  • Peer Reviewed
• [Journal Article] Regulation by afadin of cyclical activation and inactivation of Rap1, Rac1, and RhoA small G proteins at leading edges of moving NIH3T3 cells. (2009)
  • Author(s): Miyata M, Rikitake Y, Takahashi M, Nagamatsu Y, Yamauchi Y, Ogita H, Hirata K, Takai Y.
  • Journal Title: J Biol Chem. 284(36) Pages: 24595-24609
  • Peer Reviewed
• [Journal Article] The adenomatous polyposis coli-associated exchange factors Asef and Asef2 are required for adenoma formation in ApcMin/+ mice. (2009)
  • Author(s): Kawasaki Y, Tsuji S, Muroya K, Furukawa S, Shibata Y, Okuno M, Ohwada S, Akiyama T.
  • Journal Title: EMBO Rep. 10(12) Pages: 1355-1362
  • Peer Reviewed
• [Journal Article] aPKCλ/ιpromotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6. (2009)
  • Author(s): Ishiguro H, Akimoto K, Nagashima Y, Kojima Y, Sasaki T, Ishiguro-Imagawa Y, Nakaigawa N, Ohno S, Kubota Y, Uemura H.
  • Journal Title: Proc Natl Acad Sci USA. 106(38) Pages: 16369-16374
  • Peer Reviewed
• [Journal Article] The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that regulates cell migration. (2009)
  • Author(s): Itoh T, Hasegawa J, Tsujita K, Kanaho Y, Takenawa T.
  • Journal Title: Sci Signal. 2(87) Pages: ra52
  • Peer Reviewed
• [Journal Article] An essential role of the universal polarity protein, aPKCλ, on the maintenance of podocyte slit diaphragms. (2009)
  • Author(s): Hirose T, Satoh D, Kurihara H, Kusaka C, Hirose H, Akimoto K, Matsusaka T, Ichikawa I, Noda T, Ohno S.
  • Journal Title: PLoS One. 4(1) Pages: e4194
  • Peer Reviewed
• [Journal Article] A novel protein associated with membrane-type 1 matrix metalloproteinase binds p27kip1 and regulates RhoA activation, actin remodeling, and Matrigel invasion. (2009)
  • Author(s): Hoshino D, Tomari T, Nagano M, Koshikawa N, Seiki M.
  • Journal Title: J Biol Chem. 284(40) Pages: 27315-27326
  • Peer Reviewed
• [Journal Article] Both alleles of PSF1 are required for maintenance of pool size of immature hematopoietic cells and acute bone marrow regeneration. (2009)
  • Author(s): Ueno M, Itoh M, Sugihara K, Asano M, Takakura N.
  • Journal Title: Blood. 113(3) Pages: 555-562
  • Peer Reviewed
• [Journal Article] Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. (2008)
  • Author(s): Takai Y, Miyoshi J, Ikeda W, Ogita H.
  • Journal Title: Nat Rev Mol Cell Biol. 9(8) Pages: 603-615
  • Peer Reviewed
• [Journal Article] PX-RICS mediates ER-to-Golgi transport of the N-cadherin/ β-catenin complex. (2008)
  • Author(s): Nakamura T, Hayashi T, Nasu- Nishimura Y, Sakaue F, Morishita Y, Okabe T, Ohwada S, Matsuura K, Akiyama T.
  • Journal Title: Genes Dev. 22(9) Pages: 1244-1256
  • Peer Reviewed
• [Journal Article] Sequential signals toward podosome formation in NIH-src cells. (2008)
  • Author(s): Oikawa T, Itoh T, Takenawa T.
  • Journal Title: J Cell Biol. 182(1) Pages: 157-169
  • Peer Reviewed
• [Journal Article] he second dimer interface of MT1-MMP, the transmembrane domain, is essential for ProMMP-2 activation on the cell surface. (2008)
  • Author(s): Itoh Y, Ito N, Nagase H, Seiki M.
  • Journal Title: J Biol Chem. 283(19) Pages: 13053-13062
  • Peer Reviewed
• [Presentation] Phospholipid-binding proteins that induce membrane deformation. (2009)
  • Author(s): Takenawa T.
  • Organizer: Second International Conference on F-Bar proteins.
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2009-10-03
• [Presentation] Endogenous negative feedback regulation of angiogenesis by micro-RNA. (2009)
  • Author(s): 高倉伸幸
  • 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: 2009-10-02
• [Presentation] 細胞シグナリングと疾患モデルのプロテオミクス (2009)
  • Author(s): 大野茂男
  • Organizer: 日本ヒトプロテオーム機構第7回大会
  • Place of Presentation: 北里大学薬学部(東京都)
  • Year and Date: 2009-07-27
• [Presentation] 癌抑制遺伝子apcの機能 (2008)
  • Author(s): 秋山徹
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Roles of nectin and nectin-like molecule in contact inhibition of cell movement (2007)
  • Author(s): Takai Y.
  • Organizer: 6th Abercrombie Meeting on Cell Migration: from molecules to organisms.
  • Place of Presentation: Oxford, UK.
  • Year and Date: 2007-09-09
• [Book] The Sticky Synapse: Cell Adhesion Molecules and Their Role in Synapse Formation and Maintenance. (2009)
  • Author(s): T ogashi H, Ogita H, Takai Y.
  • Total Pages: 185-206
  • Publisher: Springer
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/mcb/index.html
• [Remarks]
  • URL: http://www-user.yokohama-cu.ac.jp/~ohnos/Japanease/indexJ.html
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/lipid/
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/cancercell/index.html
• [Remarks]
  • URL: http://st.biken.osaka-u.ac.jp/
• [Patent(Industrial Property Rights)] アポトーシス誘導遺伝子およびその利用 (2004)
  • Inventor(s): 秋山徹、廣子貴俊
  • Industrial Property Rights Holder: 大正製薬株式会社、秋山徹
  • Industrial Property Number: 特許第4429269号
  • Filing Date: 2004-02-10