Roles and Regulatory Mechanisms of Extracellular Matrix Remodeling in vivo

2009 Fiscal Year Final Research Report

• Project/Area Number: 16GS0311
• Research Category: Grant-in-Aid for Creative Scientific Research
• Allocation Type: Single-year Grants
• Research Institution: Kyoto University
• Principal Investigator: NODA Makoto Kyoto University, 医学研究科, 教授 (30146708)
• Co-Investigator(Kenkyū-buntansha): KITAYAMA Hitoshi 京都大学, 医学研究科, 助教授 (30231286) ; MATSUZAKI Tomoko 京都大学, 医学研究科, 助教 (50402855) ; YOSHIDA Yoko 京都大学, 医学研究科, 助教 (60130324) ; IMAMURA Yukio 京都大学, 医学研究科, 助教 (90447954)
• Co-Investigator(Renkei-kenkyūsha): MATSUZAKI Tomoko 京都大学, 医学研究科, 助教 (50402855) ; YOSHIDA Yoko 京都大学, 医学研究科, 助教 (60130324) ; IMAMURA Yukio 京都大学, 医学研究科, 助教 (90447954)
• Project Period (FY): 2004 – 2009
• Keywords: がん / 発生 / マウス遺伝学 / MMP / ADAM / Notch / シグナル伝達

Research Abstract

RECK, first isolated as a transformation suppressor gene, encodes a membrane-anchored glycoprotein essential for mouse embryogenesis and down-regulated in various type of human cancer. Our studies at the molecular, cellular, and whole animal levels revealed that RECK forms cowbell-shaped dimer, regulates a wide spectrum of extracellular metalloproteases, and protects cell surface molecules as well as extracellular matrix components. We also found that RECK expression is under dynamic regulations by various external stimuli, including growth factors, cell density, and oxygen concentration.

Research Products

• [Journal Article] Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs. (2010)
  • Author(s): Loayza-Puch F, Yoshida Y, Matsuzaki T, Takahashi C, Kitayama H., Noda M.
  • Journal Title: Oncogene 29 Pages: 2638-2648
  • Peer Reviewed
• [Journal Article] The beta1-integrin-dependent function of RECK in physiologic and tumor angiogenesis. (2010)
  • Author(s): Miki T, Shamma A, Kitajima S, Takegami Y, Noda M, Nakashima Y, Watanabe K, Takahashi C
  • Journal Title: Mol Cancer Res 8 Pages: 665-676
  • Peer Reviewed
• [Journal Article] RECK Is Up-Regulated and Involved in Chondrocyte Cloning in Human Osteoarthritic Cartilage. (2010)
  • Author(s): Kimura T, Okada A, Yatabe T, Okubo M, Toyama Y, Noda M., Okada Y.
  • Journal Title: Am J Pathol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation. (2009)
  • Author(s): Shamma A, Takegami Y, Miki T, Kitajima S, Noda M., Obara T, Okamoto T, Takahashi C
  • Journal Title: Cancer Cell 15 Pages: 255-269
  • Peer Reviewed
• [Journal Article] RECK forms cowbell-shaped dimers and inhibits matrix metalloproteinase-catalyzed cleavage of fibronectin. (2009)
  • Author(s): Omura A, Matsuzaki T, Mio K, Ogura T, Yamamoto M, Fujita A, Okawa K, Kitayama H,, Takahashi C, Sato C, Noda M.
  • Journal Title: J Biol Chem 284 Pages: 3461-3469
  • Peer Reviewed
• [Journal Article] The membrane-anchored metalloproteinase regulator RECK stabilizes focal adhesions and anterior-posterior polarity in fibroblasts. (2009)
  • Author(s): Morioka Y, Monypenny J, Matsuzaki T, Shi S, Alexander DB, Kitayama H., Noda M.
  • Journal Title: Oncogene 28 Pages: 1454-1464
  • Peer Reviewed
• [Journal Article] Density-and serum-dependent regulation of the Reck tumor suppressor in mouse embryo fibroblasts. (2009)
  • Author(s): Hatta M, Matsuzaki T, Morioka Y, Yoshida Y, Noda M.
  • Journal Title: Cell Signal 21 Pages: 1885-1893
  • Peer Reviewed
• [Journal Article] Isolation of hyperactive mutants of mammalian target of rapamycin. (2008)
  • Author(s): Ohne Y, Takahara T, Hatakeyama R, Matsuzaki T, Noda M., Mizushima N, Maeda T
  • Journal Title: J Biol Chem 283 Pages: 31861-31870
  • Peer Reviewed
• [Journal Article] Stetler-Stevenson WG, Oh J. TGF-beta signaling preserves RECK expression in activated pancreatic stellate cells. (2008)
  • Author(s): Lee H, Lim C, Lee J, Kim N, Bang S, Min B, Park G, Noda M.
  • Journal Title: J Cell Biochem 104 Pages: 1065-1074
  • Peer Reviewed
• [Journal Article] Localization of the membrane-anchored MMP-regulator RECK at the neuromuscular junctions. (2008)
  • Author(s): Kawashima S, Imamura Y, Chandana EP, Noda T, Takahashi R, Adachi E, Takahashi C, Noda M.
  • Journal Title: J Neurochem 104 Pages: 376-385
  • Peer Reviewed
• [Journal Article] Identification of Rgl3 as a potential binding partner for Rap-family small G-proteins and profilin II. (2007)
  • Author(s): Xu J, Shi S, Matsumoto N, Noda M., Kitayama H
  • Journal Title: Cell Signal 19 Pages: 1575-1582
  • Peer Reviewed
• [Journal Article] Recklessness as a hallmark of aggressive cancer. (2007)
  • Author(s): Noda M., Takahashi C.
  • Journal Title: Cancer Sci 98 Pages: 1659-1665
  • Peer Reviewed
• [Journal Article] RECK modulates Notch signaling during cortical neurogenesis by regulating ADAM10 activity. (2007)
  • Author(s): Muraguchi T, Takegami Y, Ohtsuka T, Kitajima S, Chandana EP, Omura A, Miki T, Takahashi R, Matsumoto N, Ludwig A, Noda M., Takahashi C.
  • Journal Title: Nat Neurosci 10 Pages: 838-845
  • Peer Reviewed
• [Journal Article] The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) interacts with membrane type 1 matrix metalloproteinase and CD13/aminopeptidase N and modulates their endocytic pathways. (2007)
  • Author(s): Miki T, Takegami Y, Okawa K, Muraguchi T, Noda M., Takahashi C.
  • Journal Title: J Biol Chem 282 Pages: 12341-12352
  • Peer Reviewed
• [Journal Article] Dual effects of the membrane-anchored MMP regulator RECK on chondrogenic differentiation of ATDC5 cells. (2007)
  • Author(s): Kondo S, Shukunami C, Morioka Y, Matsumoto N, Takahashi R, Oh J, Atsumi T, Umezawa A, Kudo A, Kitayama H,, Hiraki Y, Noda M.
  • Journal Title: J Cell Sci 120 Pages: 849-857
  • Peer Reviewed
• [Journal Article] Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity. (2007)
  • Author(s): Ihara M, Yamasaki N, Hagiwara A, Tanigaki A, Kitano A, Hikawa R, Tomimoto H, Noda M., Takanashi M, Mori H, Hattori N, Miyakawa T, Kinoshita M
  • Journal Title: Neuron 53 Pages: 519-533
  • Peer Reviewed
• [Journal Article] Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor. (2006)
  • Author(s): Takahashi C, Contreras B, Iwanaga T, Takegami Y, Bakker A, Bronson RT, Noda M., Loda M, Hunt JL, Ewen ME
  • Journal Title: Nat Genet 38 Pages: 118-123
  • Peer Reviewed
• [Journal Article] Stetler-Stevenson WG. TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118. (2006)
  • Author(s): Oh J, Diaz T, Wei B, Chang H, Noda M.
  • Journal Title: Oncogene 25 Pages: 4230-4234
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. (2006)
  • Author(s): Nakaji K, Ihara M, Takahashi C, Itohara S, Noda M., Takahashi R, Tomimoto H
  • Journal Title: Stroke 37 Pages: 2816-2823
  • Peer Reviewed
• [Journal Article] Stetler-Stevenson WG, Oh J. TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling. (2006)
  • Author(s): Chang H, Lee J, Poo H, Noda M., Diaz T, Wei B
  • Journal Title: Biochem Biophys Res Commun 345 Pages: 1201-1206
  • Peer Reviewed
• [Journal Article] Prognostic significance of reversion-inducing cysteine-rich protein with Kazal motifs expression in resected pathologic stage IIIA N2 non-small-cell lung cancer. (2005)
  • Author(s): Takenaka K, Ishikawa S, Yanagihara K, Miyahara R, Hasegawa S, Otake Y, Morioka Y, Takahashi C, Noda M., Ito H, Wada H, Tanaka F
  • Journal Title: Ann Surg Oncol 12 Pages: 817-824
  • Peer Reviewed
• [Journal Article] Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa. (2005)
  • Author(s): Ihara M, Kinoshita A, Yamada S, Tanaka H, Tanigaki A, Kitano A, Goto M, Okubo K, Nishiyama H, Ogawa O, Takahashi C, Itohara S, Nishimune Y, Noda M., Kinoshita M
  • Journal Title: Dev Cell 8 Pages: 343-352
  • Peer Reviewed
• [Journal Article] The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors. (2005)
  • Author(s): Echizenya M, Kondo S, Takahashi R, Oh J, Kawashima S, Kitayama H,, Takahashi C, Noda M.
  • Journal Title: Oncogene 24 Pages: 5850-5857
  • Peer Reviewed
• [Journal Article] The membraneanchored matrix metalloproteinase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator for colorectal cancer. (2004)
  • Author(s): Takeuchi T, Hisanaga M, Nagao M, Ikeda N, Fujii H, Koyama F, Mukogawa T, Matsumoto H, Kondo S, Takahashi C, Noda M., Nakajima Y
  • Journal Title: Clin Cancer Res 10 Pages: 5572-5579
  • Peer Reviewed
• [Journal Article] Expression of a novel matrix metalloproteinase regulator, RECK, and its clinical significance in resected non-small cell lung cancer. (2004)
  • Author(s): Takenaka K, Ishikawa S, Kawano Y, Yanagihara K, Miyahara R, Otake Y, Morioka Y, Takahashi C, Noda M., Wada H, Tanaka F
  • Journal Title: Eur J Cancer 40 Pages: 1617-1623
  • Peer Reviewed
• [Journal Article] Rap1 mutants with increased affinity for the guanine-nucleotide exchange factor C3G. (2004)
  • Author(s): Shi S, Noda M., Kitayama H
  • Journal Title: Oncogene 23 Pages: 8711-8719
  • Peer Reviewed
• [Journal Article] Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice. (2004)
  • Author(s): Oh J, Takahashi R, Adachi E, Kondo S, Kuratomi S, Noma A, Alexander DB, Motoda H, Okada A, Seiki M, Itoh T, Itohara S, Takahashi C, Noda M.
  • Journal Title: Oncogene 23 Pages: 5041-5048
  • Peer Reviewed
• [Journal Article] Stetler-Stevenson WG. Tissue inhibitors of metalloproteinase 2 inhibits endothelial cell migration through increased expression of RECK. (2004)
  • Author(s): Oh J, Seo DW, Diaz T, Wei B, Ward Y, Ray JM, Morioka Y, Shi S, Kitayama H, Takahashi C, Noda M.
  • Journal Title: Cancer Res 64 Pages: 9062-9069
  • Peer Reviewed
• [Journal Article] Endomucin, a sialomucin expressed in high endothelial venules, supports L-selectin-mediated rolling. (2004)
  • Author(s): Kanda H, Tanaka T, Matsumoto M, Umemoto E, Ebisuno Y, Kinoshita M, Noda M., Kannagi R, Hirata T, Murai T, Fukuda M, Miyasaka M
  • Journal Title: Int Immunol 16 Pages: 1265-1274
  • Peer Reviewed
• [Journal Article] Effects of ras and Rap1 on electrical excitability of differentiated NG108-15 cells. (2004)
  • Author(s): Imamura Y, Matsumoto N, Kondo S, Kitayama H, Noda M.
  • Journal Title: Neuroscience 127 Pages: 973-981
  • Peer Reviewed
• [Presentation] The membrane-anchored MMP-regulator Reck plays a crucial role in intussusceptive vascular remodeling. (2008)
  • Author(s): 野田亮
  • Organizer: Mechanisms&Models of Cancer
  • Place of Presentation: Cold Spring Harbor(アメリカ合衆国)
  • Year and Date: 20080814-20080817
• [Presentation] 転移/血管新生抑制タンパク質RECKの分子構造と新規機能 (2008)
  • Author(s): 大村彰
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] 細胞周期におけるRECKの役割 (2008)
  • Author(s): 吉田陽子
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] 繊維芽細胞の接着と移動におけるReckの役割 (2008)
  • Author(s): 森岡洋子
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Remarks]
  • URL: http://www.users.iimc.kyoto-u.ac.jp/~z59192/