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Professor TAKINO Takahisa
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
Kanazawa University Hospital(1990/06/01-)
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
- 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 151124 2025/01/15
- 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 38 102113 2025/03
- Claudin-11 enhances invasive and metastatic abilities of small cell lung cancer through MT1-MMP activation Sakamoto S, Inoue H, Takino T, Kohda Y, Yoshida J, Ohba S, Usami I, Suzuki T, Kawada M, Hatakeyama M. CANCER SCIENCE 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(2024)
○Molecular and Cellular Biology(2024)
○Molecular and Cellular Biology(2024)
○Molecular and Cellular Biology(2024)
○Molecular and Cellular Biology(2024)
○Molecular and Cellular Biology(2024)
○Molecular and Cellular Biology(2024)
○Molecular and Cellular Biology(2024)
○Molecular and Cellular Biology(2024)
○Molecular and Cellular Biology(2024)
○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)
Classes (Graduate Schools)
○Tumor cell biology(2024)
○Tumor cell biology(2024)
○An Introduction to Cellular Function(2017)
○An Introduction to Cellular Function(2017)
○An Introduction to Cellular Function(2016)
○An Introduction to Cellular Function(2016)