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Researcher Information

last modified：2024/12/18

Professor　TAKINO Takahisa

Mail

Faculty, Affiliation

Institute of Liberal Arts and Science

College and School Educational Field

Division of Pharmacy, Graduate School of Medical Science
Division of Natural System, Graduate School of Natural Science and Technology

Laboratory

Tumor Cell Biology　TEL:076-264-6712　FAX:

Academic Background

【Academic background(Doctoral/Master's Degree)】
Kanazawa University　Doctor　Graduate School, Division of Medicine　1995　Completed
【Academic background(Bachelor's Degree)】
The University of Tokushima　199003

Career

Japan Society for Promotion of Science(1995/04/01-1997/03/31)
National Institutes of Health(1997/04/01-1997/12/31)
Japan Society for Promotion of Science(1998/01/01-1999/09/30)
Kanazawa University　Cancer Research Institute(1999/10/01-2003/04/30)
Kanazawa University　Cancer Research Institute(2003/05/01-)
Kanazawa University　Institute of Liberal Arts and Science(2016/04/01-)

Year & Month of Birth

Academic Society

Japanese Cancer Association
Japanese Association for Metastasis Research Society
Japanese Society for Connective Tissue Research
Japanese Biochemical Society

Award

Japanese Biochemical Society
Japanese Biochemical Society
Japanese Biochemical Society

Specialities

Pathological medical chemistry、Experimental pathology

Speciality Keywords

cancer cell, invasion, metastasis, extracellular matrix, matrix metalloproteinase, signal transduction

Research Themes

Molecular Mechanism of Cancer Cell Invasion

Accumulation of mutation in oncogenes and tumor suppressor genes in normal cells results in malignant tumors. Malignant tumors invade into tissues and finally metastasize to distant organs. The goal of our project is to elucidate the molecular mechanism of tumor metastasis and develop diagnostic and therapeutic application.
　Tumor invasion into tissue requires degradation of tissue basement membrane. We discovered a protease which is the key enzyme for tumor metastasis, and named it as MT1-MMP (Nature, 1994). Accumulating evidences indicate that MT1-MMP plays important roles in not only tumor invasion but also regulation of signal transductions which induce tumor growth and migration.

Books

Papers

  • 　Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130cas.　Tamura M, Gu J, Takino T, Yamada KM. 　CANCER RESEARCH　59　2　442-449　1999/01
  • 　PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway.　Tamura M, Gu J, Danen JHE, Takino T, Miyamoto S, Yamada KM. 　JOURNAL OF BIOLOGICAL CHEMISTRY　274　29　20693-206703　1999/07
  • 　Shc and FAK differentially regulate cell motility and directionality modulated by PTEN.　Gu J, Tamura M, Pankov R, Danen JHE, Takino T, Matsumoto K, Yamada KM. 　JOURNAL OF CELL BIOLOGY　146　2　389-403　1999/07
  • 　Claudin promotes activation of pro-matrix metalloproteinase -2 mediated by membrane-type matrix metalloproteinases.　Miyamori H, Takino T, Kobayashi Y, Tokai H, Itoh Y, Seiki M, Sato H. 　JOURNAL OF BIOLOGICAL CHEMISTRY　276　30　28204-28211　2001/07
  • 　Suppression of membrane-type 1 matrix metalloproteinase (MMP)-mediated MMP-2 activation and tumor invasion by testican 3 and its splicing variant gene product, N-Tes.　Nakada M, Yamada A, Takino T, Miyamori H, Takahashi T, Yamashita J, Sato H.　CANCER RESEARCH　61　24　8896-8902　2001/12

show all

  • 　Expression of dominant negative form of Ets-1 suppresses fibronectin-stimulated cell adhesion and migration through down-regulation of integrin alpha 5 expression in U251 glioma cell line.　Kita D, Takino T, Nakada M, Takahashi T, Yamashita J, Sato H. 　CANCER RESEARCH　61　21　7985-7991　2001/11
  • 　A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine-phosphorylated　Takino T , Yoshioka K, Miyamori H, Yamada KM, Sato H. 　ONCOGENE　21　42　6488-6497　2002/10
  • 　Tetraspanin CD63 promotes targeting and lysosomal proteolysis of membrane-type 1 matrix metalloproteinase.　Takino T, Miyamori H, Kawaguchi N, Uekita T, Seiki M, Sato H. 　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　304　1　160-166　2003/04
  • 　Cleavage of syndecan-1 by membrane-type matrix metalloproteinase-1 stimulates cell migration.　Endo K, Takino T, Miyamori H, Kinsen H, Yoshizaki T, Furukawa M, Sato H. 　JOURNAL OF BIOLOGICAL CHEMISTRY　278　42　40764-40770　2003/10
  • 　CrkI adaptor protein modulates cell migration and invasion in glioblastoma　Takino T , Nakada M, Miyamori H, Yamashita J, Yamada KM, Sato H. 　CANCER RESEARCH　63　9　2335-2337　2003/06
  • 　Tyrosine phosphorylation of the CrkII adaptor protein modulates cell migration　Takino T, Tamura M, Miyamori H, Araki M, Matsumoto K, Sato H, Yamada KM.　JOURNAL OF CELL SCIENCE　116　15　3145-3155　2003/08
  • 　Cleavage of metastasis suppressor gene product KiSS-1 protein/Metastin by matrix metalloproteinases.　Takino T, Koshikawa N, Miyamori H, Tanaka M, Sasaki T, Okada Y, Seiki M, Sato H. 　ONCOGENE　22　30　4617-4626　2003/07
  • 　Cleavage of lumican by membrane-type matrix metalloproteinase-1 abrogates this proteoglycan-mediated suppression of tumor cell colony formation in soft agar.　Li Y, Aoki T, Mori Y, Ahmad M, Miyamori H, Takino T, Sato H. 　CANCER RESEARCH　64　19　7058-7064　2004/10
  • 　Membrane-type1 matrix metalloproteinase regulates collagen-dependent mitogen- activated protein/extracellular signal-regulated kinase activation and cell migration　Takino T, Miyamori H, Watanabe Y, Yoshioka K, Seiki M, Sato H.　CANCER RESEARCH　64　1044-1049　2004/02
  • 　JSAP1/JIP3 cooperates with FAK to regulate c-Jun N-terminal kinase and cell migration.　Takino T , Nakada M, Miyamori H, Watanabe Y, Sato T, Gantulga D, Yoshioka K, Yamada KM, Sato H.　JOURNAL OF BIOLOGICAL CHEMISTRY　280　45　37772-37781　2005/11
  • 　Membrane-type 1 matrix metalloproteinase modulates focal adhesion stability and cell migration.　Takino T , Watanabe Y, Matsui M, Miyamori H, Kudo T, Seiki M, Sato H. 　EXPERIMENTAL CELL RESEARCH　312　8　1381-1389　2006/03
  • 　Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 level.　Kudo T, Takino T, Miyamori H, Thompson EW, Sato H. 　CANCER SCIENCE　98　4　563-568　2007/04
  • 　Regulation of N-cadherin- based cell-cell interaction by JSAP1 scaffold in PC12h cells.　Bayarsaikhan M, Takino T, Gantulga D, Sato H, Ito T, Yoshioka K. 　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　353　2　357-362　2007/02
  • 　Inhibition of membrane-type 1 matrix metalloproteinase at cell-matrix adhesions.　Takino T , Saeki H, Miyamori H, Kudo T, Sato H.　CANCER RESEARCH　67　24　11621-11629　2007/12
  • 　Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for proMMP-2 generates active MMP-2. 　Nishida Y, Miyamori H, Thompson EW, Takino T, Endo Y, Sato H　CANCER RESEARCH　68　9096　2008
  • 　MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimentional collagen matrix　Takino T, Tsuge H, Ozawa T, Sato H.　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　396　1042-1047　2010/05
  • 　GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloproteinase. 　Sakr M, Takino T, Domoto T, Nakano H, Wong R, Sasaki M, Nakanuma Y, Sato H　CANCER SCIENCE　101　2368-2374　2010
  • 　Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly to promote cell motility　Takino T , Nagao R, Manabe R, Domoto T, Sekiguchi K, Sato H.　FEBS LETTERS　585　3378-3384　2011/10
  • 　Shedding of kidney injury molecule-1 by membrane-type 1 matrix metalloproteinase.　Guo L, Takino T, Endo Y, Domoto T, Sato H　JOURNAL OF BIOCHEMISTRY　152　425-432　2012
  • 　Cleavage of hepatocyte growth factor activator inhibitor-1 by membrane-type MMP-1 activates matriptase. 　Domoto T, Takino T, Guo LY, Sato H　CANCER SCIENCE　103　448-454　2012
  • 　Integrin α3 is overexpressed in glioma stem-like cells and promotes invasion. 　Nakada M, Nambu E, Furuyama N, Yoshida Y, Takino T, Hayashi Y, Sato H, Sai Y, Tsuji T, Miyamoto KI, Hirao A, Hamada JI.　BRITISH JOURNAL OF CANCER　108　2516-2524　2013
  • 　Aberrant glycogen synthase kinase 3β is involved in pancreatic cancer cell invasion and resistance to therapy. 　Kitano A, Shimasaki T, Chikano Y, Nakada M, Hirose M, Higashi T, Ishigaki Y, Endo Y, Takino T, Sato H, Sai Y, Miyamoto K, Motoo Y, Kawakami K, Minamoto T　PLoS One　e55289　2013
  • 　MT1-MMP prevents growth inhibition by three dimensional fibronectin matrix. 　Takino T, Guo L, Domoto T, Sato H. 　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　436　503-508　2013/07
  • 　Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with patient survival　Teng L, Nakada M, Furuyama N, Sabit H, Furuta T, Hayashi Y, Takino T, Dong Y, Sato H, Sai Y, Miyamoto KI, Berens ME, Zhao SG, Hamada JI.　NEURO-ONCOLOGY　15　12　1710-1720　2013/12/01
  • 　Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway　Yoshimoto T, Takino T , Li Z, Domoto T, Sato H.　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　455　42067　251-255　2014/12/12
  • 　Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly and N-cadherin adhesion. 　Takino T, Yoshimoto T, Nakada M, Li Z, Domoto T, Kawashiri S, Sato H　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　450　1016-1020　2014
  • 　Glycogen synthesis 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1 and c-Jun N-terminal kinase-mediated pathway. 　Chikano Y, Domoto T, Furuta T, Sabit H, Kitano-Tamura A, Pyko IV, Takino T, Sai Y, Hayashi Y, Sato H, Miyamoto KI, Nakada M, Minamoto T　MOLECULAR CANCER THERAPEUTICS　14　564-574　2015
  • 　Activation of MMP-9 by membrane type-1 MMP/MMP-2 axis stimulates tumor metastasis　Li Z, Takino T, Endo Y, Sato H　CANCER SCIENCE　108　3　347-353　2017/04/04
  • 　 Design and synthesis of novel anti-metastatic hypoxic cytotoxin TX-2137 targeting Akt kinase.　Shiba I, Kouzaki R, Yamada H, Endo Y, Takino T, Sato H, Kitazato K, Kageji T, Nagahiro S, Uto Y.　ANTICANCER RESEARCH　37　7　3877-2884　2017/07
  • 　Simple and cost-effective assay for isolating invasive living cells.　Takino T, Sato H, Seiki M.　BIOTECHNIQUES　65　3　137-142　2018/09/18
  • 　A novel celecoxib analog UTX-121 inhibits HT1080 cell invasion by modulating membrane-type 1 matrix metalloproteinase.　Yamahana H, Takino T, Endo Y, Yamada H, Suzuki T, Uto Y.　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　521　1　137-144　2020/01/01
  • 　The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through the regulation of JUNB.　Wanna-udom S, Terashima M, Lyu H, Ishimura A, Takino T, Sakari M, Tsukahara T, Suzuki T　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　524　1　150-155　2020/03/26
  • 　Isolation of highly migratory and invasive cells in three-dimensional gels. 　Takino T, Suzuki T, Seiki M.　CURRENT PROTOCOLS IN CELL BIOLOGY　86　1　e103　2020/03
  • 　KDM2B is involved in the epigenetic regulation of TGF-beta-induced epithelial-mesenchymal transition in lung and pancreatic cancer cell lines. 　Wanna-udom S, Terashima M, Ishimura A, Lyu H, Suphakphong K, Takino T, Suzuki T.　JOURNAL OF BIOLOGICAL CHEMISTRY　296　100213　2021
  • 　TGF-beta1 facilitates MT1-MMP-mediated proMMP-9 activation and invasion in oral squamous cell carcinoma cells.　Yamahana H,　Terashima M, Takatsuka R, Asada C, Suzuki T, Uto Y, Takino T　BIOCHEMISTRY AND BIOPHYSICS REPORTS　27　101072　2021/09
  • 　Structure-activity relationships of UTX-121 derivatives for the development of novel matrix metalloproteinase-2/9 inhibitors.　Yamahana H, Komiya Y, Takino T, Endo Y, Yamada H, Asada C, Uto Y. 　CHEMICAL AND PHAMACEUTICAL BULLETIN　69　10　1017-1028　2021/10/01
  • 　m6A RNA methylation regulates the transcription factors JUN and JUNB in TGF-beta-induced epithelial-mesenchymal transition of lung cancer cells　Suphakhong K, Terashima M, Wanna-Udom S, Takatsuka R, Ishimura A, Takino T, Suzuki T　JOURNAL OF BIOLOGICAL CHEMISTRY　298　11　102554　2022/10/26
  • 　ASH2L, a COMPASS core subunit, is involved in the cell invasion and migration of triple-negative breast cancer cells through the epigenetic control of histone H3 lysine 4 methylation　Batbayar G, Ishimura A, Lyu H, Wanna-Udom S, Meguro-Horike M, Terashima M, Horike S, Takino T, Suzuki T　BIOCHEMICAL AND BIOPHYSICL RESEARCH COMMUNICATIONS　669　19-29　2023/08/20
  • 　Development of UTX-143, a selective sodium-hydrogen exchange subtype 5 inhibitor, using amiloride as a lead compound　Shinohara Y, Komiya Y, Morimoto K, Endo Y, Terashima M, Suzuki T, Takino T, Ninomiya I, Yamada H, Uto Y. 　BIOORGANIC & MEDICAL CHEMISTRY　99　117603　2024/01/14
  • 　Metformin suppresses esophageal cancer progression through the radiation‑induced cellular senescence of cancer‑associated fibroblasts.　Sugimoto Y, Okamoto K, Saito H, Yamaguchi T, Kinoshita J, Nakamura K, Takino T, Endo Y, Ninomiya I, Ohta T, Inaki N.　ONCOLOGY REPORTS　52　4　129　2024/10/09
  • 　Iron regulates MT1-MMP-mediated proMMP-2 activation and cancer cell invasion　Takatsuka R, Terashima M, Ishimura A, Suzuki T, Takino T　BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　742　2025/01
  • 　m6A reader IGF2BP3 contributes to Gefitinib resistance in lung adenocarcinoma cells by modulating SNAI2 expression. 　Takatsuka R, Suzuki R, Terashima M, Suphakhong K, Takino T, Kawashiri S, Suzuki T　GENE REPORTS　2025

Conference Presentations

Others

Arts and Fieldwork

Patent

Theme to the desired joint research

Grant-in-Aid for Scientific Research

○「膜型メタロプロテイナーゼ(MFMMP)と乳癌の転移」(1995-1997)　
○「形態形成過程におけるMT1-MMPの機能発現制御機構の解析」(1999-2003)　
○「がん浸潤における細胞運動とMT-MMP発現の協調的制御機構の解析」(2000-2000)　
○「癌細胞運動とマトリックスメタロプロテアーゼ活性発現調節機構の解明」(2000-2001)　
○「がん浸潤における細胞運動とMMP発現の協調的制御機構の解析」(2001-2001)　
○「癌浸潤における細胞運動とMT-MMPの協調的制御機構の解析」(2002-2002)　
○「がん細胞運動とマトリックスメタロプロテアーゼ活性発現の調節機構の解析」(2002-2003)　
○「癌転移における膜型マトリックスメタロプロテアーゼの新規機能の解析」(2002-2003)　
○「癌細胞浸潤における細胞運動とMT-MMPの協調的制御機構の解析」(2003-2003)　
○「がん浸潤の細胞運動と細胞外マトリックス分解御機構の解析」(2004-2004)　
○「JNK結合分子による細胞運動極性制御機構の解析」(2004-2005)　
○「組織破壊に関わるマトリックスメタロプロテアーゼの機能解析」(2005-2006)　
○「JNK結合分子による細胞接着斑と運動極性形成制御機構の解析」(2006-2007)　
○「膜型マトリックスメタロプロテアーゼによる組織破壊機構の解析」(2007-2008)　
○「細胞外微小環境変化と細胞運動誘導」(2008-2010)　
○「膜型マトリックスメタロプロテアーゼによる細胞運動極性制御機構」(2008-2009)　
○「膜型マトリックスメタロプロテアーゼ-1のがん悪性化形質に果たす役割の解析」(2009-2011)　
○「細胞外マトリックス分解と細胞運動の極性形成維持機構」(2011-2013)　
○「肝細胞がんの多様性・変幻性におけるMT1-MMP依存性分子経路の解析」(2016-2018)　
○「消化器癌におけるNa+/H+交換予想体５の機能解析と特異的阻害薬の開発 」(2020-2022)　
○「がん細胞と線維芽細胞の相互教育プログラムの解明」(2021-2023)　

Competitive research funding,Contribution

Collaborative research,Consignment study

Classes (Bachelors)

○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2023)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2022)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)
○Molecular and Cellular Biology(2021)

Classes (Graduate Schools)

○An Introduction to Cellular Function(2017)
○An Introduction to Cellular Function(2017)
○An Introduction to Cellular Function(2016)
○An Introduction to Cellular Function(2016)

International Project

International Students

Lecture themes

Others (Social Activities)

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