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病理病態学腫瘍病理学/分子病理学(病理学第二)

概要

当教室の歴史は昭和14年に名古屋帝国大学の創立に伴って設置された旧病理学第二講座にさかのぼります。大島福造教授(初代教授/発がんウィルスによる家鶏肉腫の発生の研究)、田内久教授(昭和33年就任/肺がんおよび老化の研究)、星野宗光教授(昭和53年就任/電子顕微鏡を用いたがん病理およびマウス乳がんウィルスの研究)、松山睦司教授(平成元年就任/独自の胸腺腫発生ラットを用いた胸腺腫の研究)によって病理学研究の志と伝統が継承され、平成8年には先代の髙橋雅英教授(名古屋大学名誉教授・現藤田医科大学)が就任しました。髙橋教授は1985年に自ら同定したRETがん遺伝子の機能解析を基軸に、がん関連遺伝子群による発がん機構や神経系の発生に関する研究を展開しました。本研究は多発性内分泌腫瘍症2型やヒルシュスプルング病等の病態解明にもつながっています。当教室の現在の研究プロジェクトもRET下流のシグナル伝達機構の研究から発展した内容となっています。

 令和2年からは榎本篤が当研究室を主宰しており、病理専門医の育成と、少しでもオリジナルな病理学研究の展開を目標に日々努力しています。病理専門医の育成については、名古屋大学医学部附属病院病理部および関連病院の諸先生方の多大なご協力をいただいており、地域医療に貢献できる病理医の育成のみならず、サブスペシャリティを有する人材の育成に向けた取り組みも重要と考えています。
 また大学院での研究活動を通して、形態学にもとづいたリサーチクエスチョンを自ら設定できる病理医の育成を目標とし、分子の機能解析と形態学を基軸にしたアプローチを中心に、多様なバックグランドをもつメンバーにより研究をすすめています。関連病院の諸先生方および名古屋大学内外の多方面の共同研究の先生方によって当研究室は支えられており、この場を借りてお礼申し上げます。当研究室にご興味のある方は是非ご連絡ください。

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研究プロジェクト

  1. Akt基質GirdinGPIアンカー分子CD109が関わる生命現象の理解とその分子メカニズム

これまでRet等の増殖因子受容体の下流で活性化するAktキナーゼの基質としてGirdinGirders of actin filament)を、また同受容体の下流で発現が増強する分子としてCD109を同定し、それらの機能に関する研究を展開してきました。Girdinはアクチン結合分子あるいは多くの結合分子を有するハブ分子であり、細胞の移動、極性、選択的膜輸送、代謝に関わる分子であることを報告してきました(総説: Weng et al., Cancer Sci 101:836-42, 2010)。また遺伝子改変マウスや病理組織検体の解析から、Girdinが神経芽細胞あるいはがん細胞の集団的移動あるいは浸潤(collective migrationあるいはcollective invasion)を制御する分子であることを明らかにしてきました(総説: Wang et al., Pathol Int 66:183-92, 2016)。また統合失調症の感受性遺伝子であるDISC1と結合し、海馬歯状回の神経芽細胞の適切な位置決定に関わることも示してきました。
 CD109GPIアンカー型膜分子で、正常の表皮基底細胞、筋上皮細胞、血管内皮細胞に発現していますが、多くのがんではがん細胞に高発現することが特徴です(総説: Mii et al., Pathol Int 69:249-259, 2019)。受容体やマトリックス関連分子と結合して複数の増殖因子群のシグナル伝達を調節していることがわかってきました。脳グリオーマでは、CD109は腫瘍幹細胞(brain tumor stem cell)に発現し、その幹細胞性に寄与する分子であることも明らかにしました。最近の検証ではCD109は肺腺がんの浸潤マーカーであり、間質におけるTGF-βの活性化制御因子であることがわかってきました(Taki et al., Cancer Sci 111:4616-4628, 2020)。そのため、最近では新規抗がん剤開発のための分子標的としても期待されています。現在は、これらの分子とそのファミリー分子が寄与する生命現象とそのメカニズムをさらに深く理解することを目標として研究を継続しています。

  1. Stromal biology:間質を構成する細胞の多様性に着目したがんおよび線維化疾患の本態理解

がんの間質(=上皮細胞以外の領域)にはがん関連線維芽細胞(CAF; cancer-associated fibroblasts)が増生し、特に膵がんをはじめとした高悪性度のがんではその傾向が顕著です。また加齢、組織損傷・治癒、あるいは慢性炎症に伴う多くの臓器の機能低下も間質の線維芽細胞の増加(線維化)が鍵を握っています。近年、このような間質に増生する線維芽細胞には機能多様性があることがわかってきました(総説: Kobayashi et al., Nat Rev Gastroenterol Hepatol 16:282-295, 2019)。最近、私達は、がんの抑制、損傷組織の修復、および線維化の抑制において重要な働きをする線維芽細胞のマーカーとしてMeflinを同定しました。Meflin陽性CAFは膵がんを抑制する機能を有すること(Mizutani et al., Cancer Res 79:5367-5381, 2019; Miyai et al. Cancer Sci 111:1047-1057, 2020; Kobayashi et al., Gastroenterology 160:1224-1239, 2021)、Meflinは心筋虚血をはじめとする組織障害時の修復に重要であることを明らかにしてきました(Hara et al., Circ Res 125:414-430, 2019)。またMeflin遺伝子の欠損マウスに心不全を誘導すると、心臓の硬化を特徴とする心不全の一型(HFpEF; 左室駆出率の保たれた心不全あるいは拡張性心不全)を発症することがわかってきました(Hara et al., 2019)。今後は様々な病態における線維芽細胞の多様性とその意義についてさらに多くの分子に着目して解明をすすめるとともに、新規治療法の開発に向けた研究もすすめたいと考えています。

  1. 線維芽細胞の本態の解明とメカノパソロジー

Meflinは未分化な状態の間葉系幹細胞(MSC; mesenchymal stem cells)に特異的なマーカーとして同定された分子です(Maeda et al., Sci Rep, 6:22288, 2016; Hara et al., Genes Cells 26:495-512, 2021)。上述のように線維芽細胞の亜群にも発現しています。線維芽細胞は組織の構造維持に必須な細胞の一つですが、近年では組織幹細胞のニッチとして機能すること、あるいは各臓器の生理的機能に必須な役割を有することも示されてきました。一方、線維芽細胞の形質変化は周辺環境の硬化を誘導し、そのメカノストレスによってさらに線維芽細胞の機能や遺伝子発現が変化します。このことは様々な疾患の病態や老化のしくみと深い関連があると考えています。線維芽細胞の遺伝子発現プロファイルを検証すると、「線維芽細胞」と呼ばれている細胞の本態はまだ未解明な点が多いこともわかってきました。今後は未分化MSCや線維芽細胞の本態について、病理形態学を中心としたアプローチによって取り組んでいきたいと考えています。また、ヒトの病態をメカノストレスや硬さの観点で理解するメカノパソロジー(mechanopathology)の視点も研究に取り入れていきたいと考えています。



教員

構成員名役職所属
髙橋 雅英 名誉教授 腫瘍病理学
榎本 篤 教授 腫瘍病理学
三井 伸二 准教授 腫瘍病理学
白木 之浩 助教 腫瘍病理学
江崎 寛季 特任助教 腫瘍病理学

研究実績

  • 2021年
    1. Kozawa K, Sekai M, Ohba K, Ito S, Sako H, Maruyama T, Kakeno M, Shirai T, Kuromiya K, Kamasaki T, Kohashi K, Tanaka S, Ishikawa S, Sato N, Asano S, Suzuki H, Tanimura N, Mukai Y, Gotoh N, Tanino M, Tanaka S, Natsuga K, Soga T, Nakamura T, Yabuta Y, Saitou M, Ito T, Matsuura K, Tsunoda M, Kikumori T, Iida T, Mizutani Y, Miyai Y, Kaibuchi K, Enomoto A, Fujita Y.The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia.Curr Biol. 2021 May 28;S0960-9822(21)00625-4. doi: 10.1016/j.cub.2021.04.078.
    2. Nakahara Y, Hashimoto N, Sakamoto K, Enomoto A, Adams TS, Yokoi T, Omote N, Poli S, Ando A, Wakahara K, Suzuki A, Inoue M, Hara A, Mizutani Y, Imaizumi K, Kawabe T, Rosas IO, Takahashi M, Kaminski N, Hasegawa Y.Fibroblasts positive for meflin have anti-fibrotic property in pulmonary fibrosis.Eur Respir J. 2021 May 28:2003397. doi: 10.1183/13993003.03397-2020.
    3. Kawabata T, Suga H, Takeuchi K, Nagata Y, Sakakibara M, Ushida K, Ozone C, Enomoto A, Kawamoto I, Itagaki I, Tsuchiya H, Arima H, Wakabayashi T.A new primate model of hypophyseal dysfunction.Sci Rep. 2021 May 24;11(1):10729.
    4. Yoshioka N, Tanaka M, Ochi K, Watanabe A, Ono K, Sawada M, Ogi T, Itoh M, Ito A, Shiraki Y, Enomoto A, Ishigami M, Fujishiro M, Ogawa Y, Suganami T.The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis-associated liver tumors in a novel murine model.Biomed Pharmacother. 2021 Aug;140:111738. doi: 10.1016/j.biopha.2021.111738.
    5. Yasuda Y, Iwama S, Sugiyama D, Okuji T, Kobayashi T, Ito M, Okada N, Enomoto A, Ito S, Yan Y, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Takagi H, Hagiwara D, Goto M, Suga H, Banno R, Takahashi M, Nishikawa H, Arima H.CD4+ T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice.Sci Transl Med. 2021 May 12;13(593):eabb7495.
    6. Hara A, Kato K, Ishihara T, Kobayashi H, Asai N, Mii S, Shiraki Y, Miyai Y, Ando R, Mizutani Y, Iida T, Takefuji M, Murohara T, Takahashi M, Enomoto A.Meflin defines mesenchymal stem cells and/or their early progenitors with multilineage differentiation capacity.Genes Cells. 2021 May 7. doi: 10.1111/gtc.12855.
    7. Kobayashi H, Gieniec KA, Wright JA, Wang T, Asai N, Mizutani Y, Iida T, Ando R, Suzuki N, Lannagan TRM, Ng JQ, Hara A, Shiraki Y, Mii S, Ichinose M, Vrbanac L, Lawrence MJ, Sammour T, Uehara K, Davies G, Lisowski L, Alexander IE, Hayakawa Y, Butler LM, Zannettino ACW, Din MO, Hasty J, Burt AD, Leedham SJ, Rustgi AK, Mukherjee S, Wang TC, Enomoto A, Takahashi M, Worthley DL, Woods SL.The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis.Gastroenterology. 2021 Mar;160(4):1224-1239.e30
  • 2020年
    1. Ohara Y, Enomoto A, Tsuyuki Y, Sato K, Iida T, Kobayashi H, Mizutani Y, Miyai Y, Hara A, Mii S, Suzuki J, Yamashita K, Ito F, Motooka Y, Misawa N, Fukui T, Kawaguchi K, Yokoi K, Toyokuni S.Connective tissue growth factor produced by cancer‑associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma.Oncol Rep. 2020 Sep;44(3):838-848.
    2. Chen C, Enomoto A, Weng L, Taki T, Shiraki Y, Mii S, Ichihara R, Kanda M, Koike M, Kodera Y, Takahashi M.Complex roles of the actin-binding protein Girdin/GIV in DNA damage-induced apoptosis of cancer cells.Cancer Sci. 2020 Nov;111(11):4303-4317.
    3. Esaki N, Enomoto A, Takagishi M, Mizutani Y, Iida T, Ushida K, Shiraki Y, Mii S, Takahashi M.The Daple-CK1ε complex regulates Dvl2 phosphorylation and canonical Wnt signaling.Biochem Biophys Res Commun. 2020 Nov 12;532(3):406-413.
    4. Taki T, Shiraki Y, Enomoto A, Weng L, Chen C, Asai N, Murakumo Y, Yokoi K, Takahashi M, Mii S.CD109 regulates in vivo tumor invasion in lung adenocarcinoma through TGF-β signaling.Cancer Sci. 2020 Dec;111(12):4616-4628.
    5. Miyai Y, Esaki N, Takahashi M, Enomoto A. Cancer-associated fibroblasts that restrain cancer progression: Hypotheses and perspectives. Cancer Sci. 2020 Apr;111(4):1047-1057.
    6. Hirabayashi S, Hayashi M, Nakayama G, Mii S, Hattori N, Tanabe H, Kanda M, Tanaka C, Kobayashi D, Yamada S, Koike M, Fujiwara M, Takahashi M, Kodera Y. The Significance of Molecular Biomarkers on Clinical Survival Outcome Differs Depending on Colon Cancer Sidedness. Anticancer Res. 2020 Jan;40(1):201-211.
    7. Takagishi M, Esaki N, Takahashi K, Takahashi M. Cytoplasmic Dynein Functions in Planar Polarization of Basal Bodies within Ciliated Cells. iScience. 2020 Jun 26;23(6):101213.
    8. Sakurai Y, Ichinoe M, Yoshida K, Nakazato Y, Saito S, Satoh M, Nakada N, Sanoyama I, Umezawa A, Numata Y, Shi-Xu J, Ichihara M, Takahashi M, Murakumo Y. Inactivation of REV7 enhances chemosensitivity and overcomes acquired chemoresistance in testicular germ cell tumors. Cancer Lett. 2020 Jun 15;489:100-110.
  • 2019年
    1. Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Esaki N, Ushida K, Mii S, Shiraki Y, Ando K, Weng L, Ishihara S, Ponik SM, Conklin MW, Haga H, Nagasaka A, Miyata T, Matsuyama M, Kobayashi T, Fujii T, Yamada S, Yamaguchi J, Wang T, Woods SL, Worthley D, Shimamura T, Fujishiro M, Hirooka Y, Enomoto A, Takahashi M. Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis. Cancer Res. 2019 Oct 15;79(20):5367-5381.
    2. Li J, Enomoto A, Weng L, Sun L, Takahashi M. Dephosphorylation of Girdin by PP2A inhibits breast cancer metastasis. Biochem Biophys Res Commun. 2019 May 21;513(1):28-34.
    3. Ranjit M, Hirano M, Aoki K, Okuno Y, Ohka F, Yamamichi A, Kato A, Maeda S, Motomura K, Matsuo K, Enomoto A, Ino Y, Todo T, Takahashi M, Wakabayashi T, Kato T, Natsume A. Aberrant Active cis-Regulatory Elements Associated with Downregulation of RET Finger Protein Overcome Chemoresistance in Glioblastoma. Cell Rep. 2019 Feb 26;26(9):2274-2281.e5.
    4. Kobayashi H, Enomoto A, Woods SL, Burt AD, Takahashi M, Worthley DL. Cancer-associated fibroblasts in gastrointestinal cancer. Nat Rev Gastroenterol Hepatol. 2019 May;16(5):282-295.
    5. Ohno T, Miyasaka Y, Kuga M, Ushida K, Matsushima M, Kawabe T, Kikkawa Y, Mizuno M, Takahashi M. Mouse NC/Jic strain provides novel insights into host genetic factors for malaria research. Exp Anim. 2019 Aug 14;68(3):243-255.
    6. Mii S, Enomoto A, Shiraki Y, Taki T, Murakumo Y, Takahashi M. CD109: a multifunctional GPI-anchored protein with key roles in tumor progression and physiological homeostasis. Pathol Int. 2019 May;69(5):249-259.
    7. Hara A, Kobayashi H, Asai N, Saito S, Higuchi T, Kato K, Okumura T, Bando YK, Takefuji M, Mizutani Y, Miyai Y, Saito S, Maruyama S, Maeda K, Ouchi N, Nagasaka A, Miyata T, Mii S, Kioka N, Worthley DL, Murohara T, Takahashi M, Enomoto A. Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction. Circ Res. 2019 Aug2;125(4):414-430.
  • 2018年
    1. Nakamura N, Naruse K, Kobayashi Y, Miyabe M, Saiki T, Enomoto A, Takahashi M, Matsubara T. Chemerin promotes angiogenesis in vivo. Physiol Rep. 2018 Dec;6(24):e13962.
    2. Wang X, Enomoto A, Weng L, Mizutani Y, Abudureyimu S, Esaki N, Tsuyuki Y,Chen C, Mii S, Asai N, Haga H, Ishida S, Yokota K, Akiyama M, Takahashi M. Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization. Cancer Sci. 2018 Nov;109(11):3643-3656.
    3. Yasuda Y, Iwama S, Kiyota A, Izumida H, Nakashima K, Iwata N, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Enomoto A, Takahashi M, Arima H, Sugimura Y. Critical role of rabphilin-3A in the pathophysiology of experimental lymphocytic neurohypophysitis. J Pathol. 2018 Apr;244(4):469-478.
    4. Shindo A, Audrey A, Takagishi M, Takahashi M, Wallingford JB, Kinoshita M. Septin-dependent remodeling of cortical microtubule drives cell reshaping during epithelial wound healing. J Cell Sci. 2018 Jun 28;131(12):jcs212647.
    5. Mii S, Hoshino A, Enomoto A, Murakumo Y, Ito M, Yamaguchi A, Takahashi M. CD109 deficiency induces osteopenia with an osteoporosis-like phenotype in vivo. Genes Cells. 2018 Jul;23(7):590-598.
    6. Abudureyimu S, Asai N, Enomoto A, Weng L, Kobayashi H, Wang X, Chen C, Mii S, Takahashi M. Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure. Sci Rep. 2018 May 8;8(1):7292.
    7. Weng L, Han YP, Enomoto A, Kitaura Y, Nagamori S, Kanai Y, Asai N, An J, Takagishi M, Asai M, Mii S, Masuko T, Shimomura Y, Takahashi M. Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex. PLoS Biol. 2018 Mar 14;16(3):e2005090.
    8. Maegawa T, Miyasaka Y, Kobayashi M, Babaya N, Ikegami H, Horio F, Takahashi M, Ohno T. Congenic mapping and candidate gene analysis for streptozotocin-induced diabetes susceptibility locus on mouse chromosome 11. Mamm Genome. 2018 Apr;29(3-4):273-280.
    9. Mizutani Y, Kuga D, Iida M, Ushida K, Takagi T, Tokita Y, Takahashi M, Asai M. Use of Anti-phospho-girdin Antibodies to Visualize Intestinal Tuft Cells in Free-Floating Mouse Jejunum Cryosections. J Vis Exp. 2018 Mar 21;(133):57475.
    10. Esaki N, Ohkawa Y, Hashimoto N, Tsuda Y, Ohmi Y, Bhuiyan RH, Kotani N, Honke K, Enomoto A, Takahashi M, Furukawa K, Furukawa K. ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of
    11. GD2-positive small-cell lung cancer. Cancer Sci. 2018 Jan;109(1):141-153.
    12. Ushida K, Asai N, Uchiyama K, Enomoto A, Takahashi M.  Development of a method to preliminarily embed tissue samples using low melting temperature fish gelatin before sectioning: A technical note. Pathol Int. 2018 Apr;68(4):241-245.
  • 2017年
    1. Shiraki Y, Mii S, Enomoto A, Momota H, Han YP, Kato T, Ushida K, Kato A, Asai N, Murakumo Y, Aoki K, Suzuki H, Ohka F, Wakabayashi T, Todo T, Ogawa S, Natsume A and Takahashi M.Significance of perivascular tumour cells defined by CD109 expression in progression of glioma.J. Pathol. 243: 468-480 (2017).
    2. Takagishi, M., Sawada, M., Ohata, S., Asai, N., Enomoto, A., Takahashi, K., Weng, L., Ushida, K., Ara, H., Matsui, S., Kaibuchi, K., Sawamoto, K. and Takahashi, M.Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus.Cell Rep. 20: 960-972 (2017).
    3. Kuga, D., Ushida, K., Mii, S., Enomoto, A., Asai, N., Nagino, M., Takahashi, M. and Asai, M.Tyrosine phosphorylation of an actin-binding protein Girdin specifically marks tuft cells in human and mouse gut.J. Histochem. Cytochem. 65: 347-366 (2017).
    4. Han, Y-P., Enomoto, A., Shiraki, Y., Wang, S-Q., Wang, X., Toyokuni, S., Asai, N., Ushida, K., Hosne, A., Ohka, F., Wakabayashi, T., Ma, J., Natsume, A. and Takahashi, M.Significance of low mTORC1 activity in defining the characteristics of brain tumor stem cells.Neuro-Oncology 19: 636-647 (2017) .
  • 2016年
    1. Itoh, N., Enomoto, A., Nagai, T., Takahashi, M. and Yamada, K.Molecular mechanism linking BDNF/TrkB signaling with the NMDA receptor in memory: the role of Girdin in the CNS.Rev. Neurosci. 27: 481-490 (2016).
    2. Wang, X., Enomoto, A., Asai, N., Kato, T. and Takahashi, M.Collective invasion of cancer: Perspectives from pathology and development.Pathol. Int. 66: 183-192 (2016).
    3. Nakai, T., Kawasaki, T., Tada, T., Ishida, M., Iwakoshi, A., Enomoto, A., Okuda, S., Takahashi, M., Ambo, J.I., Sugai, T., Ohbayashi, C. and Ichihara, S.Well-differentiated neuroendocrine tumor of the breast with extensive lymphatic and vascular infiltration.Pathol. Int. 66: 706-707 (2016).
    4. Sunagawa M, Mii S, Enomoto A, Kato T, Murakumo Y, Shiraki Y, Asai N, Asai M, Nagino M, and Takahashi M.Suppression of skin tumorigenesis in CD109-deficient mice.Oncotarget 7: 82836-82850 (2016).
    5. Nogimori, K., Hori, T., Kawaguchi, K., Fukui, T., Mii, S., Nakada, H., Matsumoto, Y., Yamauchi, Y., Takahashi, M., Furukawa, K., Okajima, T., Yokoi, K., Hasegawa, Y. and Furukawa, K.Increased expression levels of ppGalNAc-T13 in lung cancers: Significance in the prognostic diagnosis.Int. J. Oncol. 49: 1369-1376 (2016) .
    6. Maeda, K., Enomoto, A., Hara, A., Asai, N., Kobayashi, T., Horinouchi, A., Maruyama, S., Ishikawa, Y., Nishiyama, T., Kiyoi, H., Kato, T., Ando, K., Weng, L., Mii, S., Asai, M., Mizutani, Y., Watanabe, O., Hirooka, Y., Goto, H. and Takahashi, M.Identification of Meflin as a potential marker for mesenchymal stromal cells.Sci. Rep. 6: 22288 (2016).
    7. Nahorski, M.S, Asai, M., Wakeling, E., Parker, A., Asai, N., Canham, N., Holder, S.E., Chen, Y.C., Dyer, J., Brady, A.F., Takahashi, M. and Woods, C.G.CCDC88A mutations cause PEHO-like syndrome in humans and mouse.Brain 139: 1036-1044 (2016).
    8. Sakakura, H., Mii, S., Hagiwara, S., Kato, T., Yamamoto, N., Hibi, H., Takahashi, M. and Murakumo, Y.CD109 is a component of exosome secreted from cultured cells.Biochem. Biophys. Res. Commun. 469: 816-822 (2016).
    9. Ara, H., Takagishi, M., Enomoto, A., Asai, M., Ushida, K., Asai, N., Shimoyama, Y., Kaibuchi, K., Kodera, Y. and Takahashi, M.Role for Daple in non-canonical Wnt signaling during gastric cancer invasion and metastasis.Cancer Sci. 107: 133-139 (2016).
  • 2015年
    1. Yamamura Y, Asai N, Enomoto A, Kato T, Mii S, Kondo Y, Ushida K., Niimi, K, Tsunoda N, Nagino M, Ichihara S, Furukawa K, Maeda K, Murohara T, Takahashi M.Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression.Cancer Res. 75: 813-823 (2015).
    2. Takashima S, Kanatsu-Shinohara M, Tanaka T, Morimoto H, Inoue K, Ogonuki N, Jijiwa M, Takahashi M, Ogura A, Shinohara T.Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal.Stem Cell Rep. 4: 489-502 (2015).
    3. Mansour MA, Hyodo T, Ito S, Kurita K, Kokuryo T, Uehara K, Nagino M, Takahashi M, Hamaguchi M, Senga, T.SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling.FEBS J. 282: 1394-1405 (2015).
    4. Omori K, Asai M, Kuga D, Ushida K, Izuchi T, Mii S, Enomoto A, Asai N, Nagino M, Takahashi M.Girdin is phosphorylated on tyrosine 1798 when associated with structures required for migration.Biochem. Biophys. Res. Commun. 458: 934-940 (2015).
    5. Zhang J-M, Murakumo Y, Hagiwara S, Jiang P, Mii S, Kalyoncu E, Saito S, Suzuki C, Sakurai Y, Numata Y, Yamamoto T, Takahashi, M.CD109 attenuates TGFbeta1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells.Biochem. Biophys. Res. Commun. 459: 252-258 (2015).
    6. Noda T, Maeda K, Hayano S, Asai N, Enomoto A, Takahashi M, Murohara, T.A new ER stress regulator, Gipie, regulates the survival of vascular smooth muscle cells and the neointima formation after vascular injury.Arterioscler. Thromb. Vasc. Biol. 35: 1246-1253 (2015).
    7. Ichimiya H, Maeda K, Enomoto A, Weng L, Takahashi M, Murohara, T.Girdin/GIV regulates transendothelial permeability by controlling VE-cadherin trafficking through the small GTPase, R-Ras.Biochem. Biophys. Res. Commun. 461: 260-267 (2015).
    8. Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H. Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y.Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitisJ. Clin. Endocrinol .Metab. 100: E946-54 (2015).
    9. Muramatsu A, Enomoto A, Kato T, Weng L, Kuroda K, Asai N, Asai M, Mii S, Takahashi M.Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin.Biochem Biophys Res Commun. 463: 999-1005 (2015).
    10. Hayano S, Takefuji M, Maeda K, Noda T, Ichimiya H, Kobayashi K, Enomoto A, Asai N, Takahashi M, Murohara, T.Akt-dependent Girdin phosphorylation regulates repair processes after acute myocardial infarction.J Mol Cell Cardiol. 88: 55-63 (2015)
  • 2014年
    1. Nakai T, Nagai T, Tanaka M, Itoh N, Asai N, Enomoto A, Asai M, Yamada S, Saifullah AB, Sokabe M, Takahashi M, Yamada, K.Girdin phosphorylation is crucial for synaptic plasticity and memory: Potential role in the interaction of BDNF/TrkB/Akt signaling with NMDA receptor.J Neurosci. 34: 14995-15008 (2014).
    2. Weng L, Enomoto A, Miyoshi H, Takahashi K, Asai N, Morone N, Jiang P, An J, Kato T, Kuroda K, Watanabe T, Asai M, Ishida-Takagishi M, Murakumo Y, Nakashima H, Kaibuchi K, Takahashi M.Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin.EMBO J. 33: 2098-2112 (2014).
    3. Ota H, Hikita T, Sawada M, Nishioka T, Matsumoto M, Komura M, Ohno A, Kamiya Y, Miyamoto T, Asai N, Enomoto A, Takahashi M, Kaibuchi K, Sobue K, Sawamoto. K.Speed control for neuronal migration in the postnatal brain by Gmip-mediated local inactivation of RhoA.Nat Commun. July 30;5:4532 (2014).
    4. Han YP, Ma CK, Wang SQ, Enomoto A, Zhao Y, Takahashi M, Ma J.Evaluation of osteopontin as a potential biomarker for central nervous system embryonal tumors.J Neuro-Oncol. 119:343-351 (2014).
    5. Kato T, Enomoto A, Watanabe T, Haga H, Ishida S, Kondo Y, Furukawa K, Urano T, Mii S, Weng L, Ishida-Takagishi M, Asai M, Asai N, Kaibuchi K, Murakumo Y, Takahashi M.TRIM27/MTRF-B-dependent integrin beta1 expression defines leading cells in cancer cell collecitives.Cell Rep. 7:1156-1167 (2014)
    6. Niimi K, Murakumo Y, Watanabe N, Kato T, Mii S, Enomoto A, Asai M, Asai N, Yamamoto E, Kajiyama H, Shibata K, Kikkawa F, Takahashi M.Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cellsCancer Sci. 105:545-552 (2014).
    7. Hagiwara D, Arima H, Morishita Y, Wenjun L, Azuma Y, Ito Y, Suga H, Goto M, Banno R, Sugimura Y, Shiota A, Asai N, Takahashi M, Oiso Y.Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus.Cell Death and Disease 5:e114 (2014).
    8. Miyachi H, Mii S, Enomoto A, Murakumo Y, Kato T, Asai N, Komori K, Takahashi M.Role of Girdin in intimal hyperplasia in vein grafts and efficacy of atelocollagen-mediated application of siRNA for vein failure.J Vasc Surg. 60:479-489.e5 (2014).
    9. Nishimae K, Tsunoda N, Yokoyama Y, Kokuryo T, Iwakoshi A, Takahashi M, Nagiono, M.The impact of Girdin expression on recurrence-free survival in patients with luminal-type breast cancer.Breast Cancer in press
    10. Qiao S, Fan K, Iwashita T, Ichihara M, Yoshino M, Takahashi M.The involvement of reactive oxygen species derived from NADPH oxidase-1 activation on the constitutive tyrosine auto-phosphorylation of RET proteins.Free Radic Res. 48:427-34 (2014).
    11. Sakakura H, Murakumo Y, Mii S, Hagiwara S, Kato T, Asai M, Hoshino A, Yamamoto N, Sobue S, Ichihara M, Ueda M, Takahashi M.Detection of a soluble form of CD109 in serum of CD109 transgenic and tumor xenografted mice.PLoS One. 9:e83385 (2014).
    12. Takahara Y, Maeda M, Hasegawa H, Ito S, Hyodo T, Asano E, Takahashi M, Hamaguchi M, Senga T.Silencing of TBC1D15 promotes RhoA activation and membrane blebbing.Mol Cell Biochem. 389:9-16 (2014).
    13. Hoshino A, Hanada S, Yamada H, Mii S, Takahashi M, Mitarai S, Yamamoto K, Manome Y.Mycobacterium tuberculosis escapes from the phagosomes of infected human osteoclasts reprograms osteoclast development via dysregulation of cytokines and chemokines.Pathog Dis. 70:28-39 (2014).
  • 2013年
    1. Ueno S, Nishiguchi KM, Tanioka H, Enomoto A, Yamanouchi T, Kondo M, Yasuma TR, Yasuda S, Kuno N, Takahashi M, Terasaki H.Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.PLoS One. 8:e81507 (2013).
    2. Ota H, Hikita T, Nishioka T, Matsumoto M, Ito J, Asai N, Enomoto A, Takahashi M, Kaibuchi K, Sobue K, Sawamoto K.Proteomic analysis of Girdin-interacting proteins in migrating new neurons in the postnatal mouse brain.Biochem Biophys Res Commun. 442:16-21 (2013).
    3. Asano E, Hasegawa H, Hyodo T, Ito S, Maeda M, Takahashi M, Hamaguchi M, Senga T.The Aurora-B-mediated phosphorylation of SHCBP1 regulates cytokinetic furrow ingression.J Cell Sci. 126:3263-3270 (2013).
    4. Hagiwara S, Yamamoto N, Furue H, Sakakura H, Shigetomi T, Murakumo Y, Hibi H, Takahashi M, Ueda M.Pathological analysis of Ki-67 and CD109 expression in tongue squamous cell carcinoma.J Oral Maxillofac Surg Med Pathol. 25:276-281 (2013).
    5. Watanabe, N., Mii, S., Asai, N., Asai, M., Niimi, K., Ushida, K., Kato, T., Enomoto, A., Ishii, H., Takahashi, M., and Murakumo, Y,The REV7 subunit of DNA polymerase ζ is essential for primordial germ cell maintenance in the mouse.J. Biol. Chem.288:10459-10471 (2013).
    6. Ito, T., Komeima, K., Yasuma, T., Enomoto, A., Asai, N., Iwase, S., Takahashi, M. and Terasaki, H.Girdin and its phosphorylation dynamically regulate neonatal vascular development and pathological neovascularization in the retina.Am. J. Pathol. 182: 586-596 (2013).
    7. An, J., Enomoto, A., Weng, L., Kato, T., Iwakoshi, A., Ushida, K., Maeda, K., Ishida-Takagishi, M., Ishii, G., Ming, S., Sun, T. and Takahashi, M.Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer.J. Cancer Res. Clin. Oncol. 139: 379-388 (2013).
  • 2012年
    1. Muteliefu G, Shimizu H, Enomoto A, Nishijima F, Takahashi M, Niwa T.Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21, and prelamin A through oxidative stress.Am J Physiol Cell Physiol. 303:C126-134 (2012).
    2. Mao, J.-Z., Jiang, P., Cui, S.-P., Ren, Y.-L., Zhao, J., Yin, X.-H., Enomoto, A., Liu, H.-J., Hou, L., Takahashi, M. and Zhang, B.Girdin locates in centrosome and midbody and plays an important role in cell division.Cancer Sci. 103: 1780-1787 (2012).
    3. Horio-Sakurai, M., Kato, T., Mii, S., Enomoto, A., Asai, M., Asai, N., Murakumo, Y., Shibata, K., Kikkawa, F. and Takahashi, M.Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer.Cancer Med. 1: 218-229 (2012).
    4. Asai M., Asai, N., Murata, A., Yokota, H., Ohmori, K., Mii, S., Enomoto, A., Murakumo, Y. and Takahashi, M.Similar Phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage.Biochem. Biophys. Res. Commun. 426: 533-538 (2012).
    5. Hyodo T, Ito S, Hasegawa H, Asano E, Maeda M, Urano T, Takahashi M, Hamaguchi M, Senga T.Misshapen-like kinase 1 (MINK1) Is a Novel Component of Striatin-interacting Phosphatase and Kinase (STRIPAK) and Is Required for the Completion of Cytokinesis.J. Biol. Chem. 287: 25019-25029 (2012).
    6. Mii, S., Murakumo, Y., Asai, N., Jijiwa, M., Hagiwara, S., Kato, T., Asai, M., Enomoto, A., Ushida, K., Sobue, S., Ichihara, M. and Takahashi, M.Epidermal hyperplasia and appendage abnormalities in mice lacking CD109.Am. J. Pathol. 181: 1180-1189 (2012).
    7. Muteliefu, G., Shimizu, H., Enomoto, A., Nishijima, F., Takahashi, M. and Niwa, T.Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21 and prelamin A through oxidative stress.Am. J. Physiol. Cell Physiol. 303: C126-C134 (2012).
    8. Ishida-Takagishi, M., Enomoto, A., Asai, N., Ushida, K., Watanabe, T., Hashimoto, T., Kato, T., Weng, L., Matsumoto, S., Asai, M., Murakumo, y., Kaibuchi, K., Kikuchi, A. and Takahashi, M.The Dvl-associated protein Daple controls the non-canonical Wnt/Rac pathway and cell motility.Nature Commun. 3: 859 (2012).
    9. Ohara, K., Enomoto, A., Kato, T., Hashimoto, T., Isotani-Sakakibara, M., Asai, N., Ishida,-Takagishi, M., Weng, L., Nakayama, M., Watanabe, T., Kato, K., Kaibuchi, K., Murakumo, Y., Hirooka, Y., Goto, H. and Takahashi M.Involvement of Girdin in the dermination of cell polarity during cell migration.PLoS One, 7: e36681 (2012).
    10. Iwakoshi A., Murakumo Y., Kato T., Kitamura A., Mii S., Saito S., Yatabe Y., Takahashi M.RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations.Pathol. Int. 62: 324-330 (2012).
    11. Natsume, A., Kato, T., Kinjo, S., Enomoto, A., Toda, H., Shimato, S., Ohka, F., Motomura, K., Kondo, Y., Miyata, T., Takahashi, M. and Wakabayashi, T.Girdin maintains the stemness of glioblastoma stem cells.Oncogene 31: 2715-2724 (2012).
    12. Ohgami, N., Ida-Eto, M., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M. and Kato, M.Partial impairment of c-Ret at tyrosine 1062 accelerates age-related hearing loss in mice.Neurobiol. Aging 33: 626 e25-34 (2012).
    13. Kee, H. J., Kim, J-R, Joung, H., Choe, N., Lee, S. E., Eom, G. H., Kim, J. C., Geyer, S. H., Jijiwa, M., Kato, T., Kawai, K., Weninger, W. J., Seo, S. B., Nam, K-I., Jeong, M. H., Takahashi, M. and Kook, H.Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb 1.Cell Death Differ. 19: 121-131 (2012).
  • 2011年
    1. Nakamura, N., Naruse, K., Kobayashi, Y., Matsuki, T., Hamada, Y., Nakashima, E., Kamiya, H., Hata, M., Nishikawa, T., Enomoto, A., Takahashi, M., Murohara, T., Matsubara, T., Oiso, Y., Nakamura, J.High glucose impairs the proliferation and increases the apoptosis of endothelial progenitor cells by suppression of Akt.J. Diabetes Invest. 2: 262-270 (2011).
    2. Asano, E., Maeda, M., Hasegawa, H., Ito, S., Hyodo, T., Yuan, H., Takahashi, H., Hamaguchi, M. and Senga, T.Role of palladin phosphorylation by extracellular signal-regulated kinase in cell migration.PLOS One 6: e29338 (2011).
    3. Morishita, Y., Arima, H., Hiroi, M., Hayashi, M., Hagiwara, D., Asai, N., Ozaki, N., Sugiura, Y., Nagasaki, H., Shiota, A., Takahashi, M. and Oiso, Y.Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum.Endocrinology 152: 4846-4855 (2011).
    4. Kuroda, K., Yamada, S., Tanaka, M., Iizuka, M., Yano, H., Mori, D., Tsuboi, D., Nishioka, T., Namba, T., Iizuka, Y., Kubota, S., Nagai, T., Ibi, D., Wang, R., Enomoto, A., Isotani-Sakakibara, M., Asai, N., Kimura, K., Kiyonari, H., Abe, T., Mizoguchi, A., Sokabe, M., Takahashi, M., Yamada, K. and Kaibuchi, K.Behavioral alterations associated with targeted disruption of exons 2 and 3 of the DISC1 gene in the mouse.Hum. Mol. Genet. 20: 4666-4683 (2011).
    5. Huang, Z., Ichihara, S., Oikawa, S., Chang, J., Zhang, L., Takahashi, M., Subramanian, K., Mohideen, S. S., Wang, Y. and Ichihara, G.Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromoprpane.Toxicol. Appl. Pharmacol. 257: 93-101 (2011).
    6. Motegi Y., Katayama K., Sakurai F., Kato T., Yamaguchi T., Matsui H., Takahashi M., Kawabata K., Mizuguchi H.An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors.J. Control Release 153: 149-153 (2011).
    7. Wang, Y., Kaneko, N., Asai, N., Enomoto, A., Isotani-Sakakibara, M., Kato, T., Asai, M., Murakumo, Y., Ota, H., Hikita, T., Namba, T., Kuroda, K., Kaibuchi, K., Ming, G., Song, H., Sawamoto, K. and Takahashi, M.Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain.J. Neurosci. 31: 8109-8122 (2011).
    8. Miyake, H., Maeda, K., Asai, N., Shibata, R., Ichimiya, H., Isotani-Sakakibara, M., Yamamura, Y., Kato, K., Enomoto, A., Takahashi, M. and Murohara, T.The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury.Circ. Res. 108: 1170-1179 (2011).
    9. Matsushita, E., Asai, N., Enomoto, A., Kawamoto, Y., Kato, T., Mii, S., Maeda, K., Shibata, R., Hattori, S., Hagikura, M., Takahashi, k., Sokabe, M., Murakumo, Y., Murohara, T. and Takahashi, M.Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cell.Mol. Biol. Cell. 22: 736-747 (2011).
    10. Miyamoto, R., Jijiwa, M., Asai, M., Kawai, K., Ishida-Takagishi, M., Mii, S., Asai, N., Enomoto, A., Murakumo, Y., Yoshimura, A. and Takahashi, M.Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant miceDev. Biol.349: 160-168 (2011).
    11. Saito, S., Murakumo, Y., Tsuzuki, T., Dambara, A., Kato, T., Enomoto, A., Asai, N., Maruyama, S., Matsuo, S. and Takahashi, M.Analysis of GDNF-inducible zinc finger protein 1 expression in human diseased kidney.Human Pathol. 42: 848-858 (2011).
  • 2010年
    1. Yamaguchi M., Suyari O., Nagai R., Takahashi M.dGirdin a new player of Akt /PKB signaling in Drosophila melanogaster.Front. Biosci. 15: 1164-1171 (2010).
    2. Hagikura, M., Murakumo, Y., Hasegawa, M., Jijiwa, M., Hagiwara, S., Mii, S., Hagikura, S., Matsukawa, Y., Yoshino, Y., Hattori, R., Wakai, K., Nakamura, S., Gotoh, M. and Takahashi, M.Correlation of pathological grade and tumor stage of urothelial carcinoma with CD109 expression.Pathol. Int. 60: 735-743 (2010).Ohgami, N., Ida-Eto, M., Shimotake, T., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M. and Kato, M.
    3. c-Ret-mediated hearing loss in mice with Hirschsprung disease.Proc. Natl. Acad. Sci. USA. 107: 13051-13056 (2010).
    4. Hagiwara, S., Murakumo, Y., Mii, S., Shigetomi, T., Yamamoto, N., Furue, H., Ueda, M. and Takahashi,M.Processing of CD109 by furin and its role in the regulation of TGF-beta signaling.Oncogene 29: 2181-2191.(2010)
    5. Kurotsuchi, A., Murakumo, Y., Jijiwa, M., Kurokawa, K., Itoh, Y., Kodama, Y., Kato, T., Enomoto, A.,Asai, N., Terasaki, H. and Takahashi, M.Analysis of DOK-6 function in downstream signaling of RET in human neuroblastoma cells.Cancer Sci. 101: 1147-1155 (2010).
    6. Weng, L., Enomoto, A., Ishida-Takagishi, M., Asai, N. and Takahashi, M.Girding for migratory cues: Role of the Akt substrate Girdin in cancer progression and angiogenesis.Cancer Sci. 101: 836-842 (2010).
    7. Kato, M., Takeda, K., Hossain, K., Thang, N.D., Kaneko, Y., Kumasaka, M., Yamanoshita, O., Uemura, N.,Takahashi, M., Ohgami, N., and Kawamoto, Y.A redox-linked novel pathway for arsenic-mediated RET tyrosine kinase activation.J. Cell. Biochem. 110: 399-407 (2010).
    8. Ohshima, Y., Yajima, I., Kumasaka, M.Y., Yanagishita, T., Watanabe, D., Takahashi, M., Inoue, Y., Ihn, H., Matsumoto, Y. and Kato, M.CD109 expression levels in malignant melanoma.J. Dermatol. Sci. 57: 140-142 (2010).
    9. Kumasaka, M.Y., Yajima, I., Hossain, K., Iida, M., Tsuzuki, T., Ohno, T., Takahashi, M., Yanagisawa,M. and Kato, M.A novel mouse model for de novo Melanoma.Cancer Res. 70: 24-29 (2010).
  • 2009年
    1. Muteliefu, G., Enomoto, A., Jiang, P., Takahashi, M., Niwa, T.Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells.Nephrol. Dial. Transplant. 24: 2051-2058 (2009).
    2. Lu, B., Cebrian, C., Chi, X., Kuure, S., Kuo, R., Bates, C.M., Arber, S., Hassell, J., MacNeil, L., Hoshi, M., Jain, S., Asai, N., Takahashi, M., Schmidt-Ott, K., Barasch, J., D'Agati, V. and Costantini, F.Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis.Nature Genet. 41:1295-1302 (2009).
    3. Puseenam, A., Yoshioka, Y., Nagai, R, Hashimoto, R, Suyari, O, Itoh, M, Enomoto, A, Takahashi, M. and Yamaguchi, M.A novel Drosophila Girdin-like protein is involved in Akt pathway control of cell size.Exp. Cell Res. 315:3370-3380 (2009).
    4. Enomoto, A., Asai, N., Namba, T., Wang, Y., Kato, T., Tanaka, M., Tatsumi, H., Taya, S., Tsuboi, D., Kuroda, K., Kaneko, N., Sawamoto, K., Miyamoto, R., Jijiwa, M., Murakumo, Y., Sokabe, M., Seki, T., Kaibuchi, K. and Takahashi, M.Roles of Disrupted-in-Schizophrenia 1-interacting protein Girdin in postnatal development of the dentate gyrus.Neuron 63: 774-787 (2009).
    5. Tsukamoto, H., Kato, T., Enomoto, A., Nakamura, N., Shimono, Y., Jijiwa, M., Asai, N., Murakumo, Y., Shibata, K., Kikkawa, F. and Takahashi, M.Expression of Ret finger protein correlates with outcomes in endometrial cancer.Cancer Sci. 100: 1895-1901 (2009).
    6. Chi, X., Michos, O., Shakya, R., Riccio, P., Enomoto, H., Licht, J.D., Asai, N., Takahashi, M., Ohgami, N., Kato, M., Mendelsohn, C. and Costantini, FRet-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis.Dev. Cell 17: 199-209 (2009).
    7. Nakamura, N., Naruse, K., Matsuki, T., Hamada, Y., Nakashima, E., Kamiya, H., Matsubara, T., Enomoto, A., Takahashi, M, Oiso, Y. and Nakamura, J.Adiponectin promotes migration activities of endothelial progenitor cells via Cdc42/Rac1FEBS Lett. 583: 2457-2463 (2009).
    8. Kato, T., Shimono, Y., Hasegawa, M., Jijiwa, M., Enomoto, A., Asai, N., Murakumo, Y. and Takahashi, M.Characterization of the HDAC1 complex that regulates the sensitivity of cancer cells to oxidative stress.Cancer Res. 69: 3597-3604 (2009).
    9. Jiang, P., Enomoto, A. and Takahashi, M.Cell biology of the movement of breast cancer cells: intracellular signaling and the actin cytoskeleton.Cancer Lett. 284:122-130 (2009).
  • 2008年
    1. Hasegawa, T., Enomoto, A., Kato, T., Kawai, K., Miyamoto, R., Jijiwa, M., Ichiahara, M., Ishida, M., Asai, N., Murakumo, Y., Ohara, K., Niwa, Y., Goto, H., and Takahashi, M.Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice.Oncogene 27: 5684-5695 (2008).
    2. Hagiwara, S., Murakumo, Y., Sato, T., Mitsudo, K., Tohnai, I., Ueda, M. and Takahashi, M.Up-regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity.Cancer Sci. 99: 1916-1923 (2008).
    3. Hasegawa, M., Moritani, S., Murakumo, Y., Sato, T., Hagiwara, S., Suzuki, C., Mii, S., Jijiwa, M., Enomoto, a., Asai, N., Ichihara, S. and Takahashi, M.CD109 expression in basal-like breast carcinoma.Pathol. Int. 58: 288-294 (2008).
    4. Kitamura, T., Asai, N., Enomoto, A., Maeda, K., Kato, T., Ishida, M., Jiang, P., Watanabe, T., Usukura, J., Kondo, T., Costantini, F., Murohara, T. and Takahashi, M.Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin.Nature Cell Biol., 10:329-337(2008).
    5. Jiang, P., Enomoto, A., Jijiwa, M., Kato, T., Hasegawa, T., Ishida, M., Sato, T., Asai, N., Murakumo, Y. and Takahashi, M.An actin-binding protein Girdin regulates the motility of breast cancer cells.Cancer Res., 68:1310-1318(2008).
    6. Jijiwa, M., Kawai, K., Fukihara, J., Nakamura, A., Hasegawa, M., Suzuki, C., Sato, T., Enomoto, A., Asai, N., Murakumo, Y. and Takahashi, M.GDNF-mediated Signaling via RET Tyrosine 1062 is Essential for Maintenance of Spermatogonial Stem Cells.Genes Cells, 13:365-374(2008).
    7. Suzuki, C., Murakumo, Y., Kawase, Y., Sato, T., Morinaga, T., Fukuda, N., Enomoto, A., Ichihara, M. and Takahashi, M.A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1.Biochem. Biophys. Res. Commun. 366: 226-232 (2008).
  • 2007年
    1. Ichihara, M., Murakumo, Y., Masuda, A., Matsuura, T., Asai, N., Jijiwa, M., Ishida, M., Shinmi, J., Yatsuya, H., Qiao, S., Takahashi, M. and Ohno, K.Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities.Nucleic Acids Res. 35: e123 (2007).
    2. Sato, T. Murakumo, Y., Hagiwara, S., Jijiwa, M., Suzuki, C. and Takahashi, M.High level expression of CD109 in lung squamous cell carcinoma.Pathol. Int. 57: 719-724 (2007).
    3. Dambara, A., Morinaga, T., Fukuda, N., Yamakawa, Y., Kato, T., Enomoto, A., Asai, N., Murakumo, Y., Matsuo, S. and Takahashi, M.Nucleolin modulates the subcellular localization of GDNF-inducible zinc finger protein 1 and its roles in transcription and cell proliferation.Exp. Cell Res. 313: 3755-3766 (2007).
    4. Murakami, M., Ichihara, M., Sobue, S., Kikuchi, R., Ito H., Kimura, A., Iwasaki, T., Takagi, A., Kojima, T., Takahashi, M., Suzuki, M., Banno, Y., Nozawa, Y. and Murate, T.RET signaling-induced SPHK1 gene expression plays a role in both GDNF-induced differentiation and MEN2-type oncogenesis.J. Neurochem. 102: 1585-1594 (2007).
    5. Li, B., Zhou, J., Hu, J., Jin, H., Shimono, Y., Takahashi, M. and Xu, G.Polycomb protein Cbx4 promotes SUMO modification of de novo DNA methyltransferase Dnmt3a.Biochem. J. 405: 369-378 (2007).
    6. Ishida, M., Ichihara, M., Mii, S., Jijiwa, M., Asai, N., Enomoto, A., Kato, T., Majima, A., Jiang, P., Murakumo, Y. and Takahashi, M.Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase.Cancer Sci. 98: 815-821 (2007).
    7. Hasegawa, M., Hagiwara, S., Sato, T., Jijiwa, M., Murakumo, Y., Maeda, M., Moritani, S., Ichihara, S. and Takahashi, M.CD109, a new marker for myoepithelial cells of mammary, salivary, and lacrimal glands and prostate basal cellsPathol. Int. 57: 245-250 (2007).
    8. Kee, H. J., Kim, J-R., Nam, K-I., Park, H. Y., Shin, S., Kim, J. C., Shimono, Y., Takahashi, M., Jeong, M. H., Kim, N., Kim, K. K. and Kook, H.Enhancer of Polycomb1, a novel homeodomain only protein binding partner, induces skeletal muscle differentiation.J. Biol. Chem. 282: 7700-7709 (2007).
    9. Kato, M., Ohgami, N., Kawamoto, Y., Tsuzuki, T., Hossain, K., Yanagishita, T., Ohshima, Y., Tsuboi, H., Yamanoshita, O., Matsumoto, Y., Takahashi, M. and Nakashima, I.Protective effect of hyperpigmented skin on UV-mediated cutaneous cancer development.J. Invest. Dermatol. 127: 1244-1249 (2007).
  • 2006年
    1. Asai, N., Fukuda, T., Wu, Z., Enomoto, A., Pachnis, V., Takahashi, M. and Costantini, F.Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells.Development 133: 4507-4516 (2006).
    2. Murakumo, Y., Jijiwa, M., Asai, N., Ichihara, M., and Takahashi, M.RET and neuroendocrine tumors.Pituitary 9: 179-192 (2006).
    3. Enomoto, A., Jiang, P., and Takahashi, M.Girdin, a novel actin-binding protein, and its family of proteins posses versatile function in the Akt and Wnt signaling pathways.Ann. NY Acad. Sci., 1086: 169-184 (2006).
    4. Kato, M., Takeda, K., Kawamoto, Y., Tsuzuki, T., Kato, Y., Ohno, T., Hossain, K., Iftakhar-E-Khuda, I., Ohgami, N., Isobe, K., Takahashi, M. and Nakashima, I.Novel hairless RET-transgenic mouse line with melanocytic nevi and anagen hair follicles.J. Invest. Dermatol. 126: 2547-2550 (2006).
    5. Uchida, M., Enomoto, A., Fukuda, T., Kurokawa, K., Maeda, K., Kodama, Y., Asai, N., Hasegawa, T., Shimono, Y., Jijiwa, M., Ichihara, M., Murakumo, Y. and Takahashi, M.Dok-4 regulates GDNF-dependent neurite outgrowth through downstream activation of Rap1 and mitogen-activated protein kinase.J. Cell Sci. 119: 3067-3077 (2006).
    6. Takeda, K., Kawamoto, Y., Okuno, Y, Kato, M., Takahashi, M., Suzuki, H., Isobe, K. and Nakashima, I.A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities.FEBS Lett. 839-843 (2006).
    7. Asai, N., Jijiwa, M., Enomoto, A., Kawai, K., Maeda, K., Ichihara, M. and Takahashi M.RET receptor signaling; Dysfunction in thyroid cancer and Hirschsprung’s disease.Pathol. Int. 56: 164-172 (2006).
    8. Murakumo, Y., Mizutani, S., Yamaguchi, M., Ichihara, M. and Takahashi, M.Analyses of ultraviolet-induced focus formation of hREV1 protein. C Genes Cells 11: 193-205 (2006).
  • 2005年
    1. Zhang JM, Hashimoto M, Kawai K, Murakumo Y, Sato T, Ichihara M, Nakamura S, Takahashi M.CD109 expression in squamous cell carcinoma of the uterine cervixPathol Int. 55: 165-169 (2005).
    2. Shimono, K., Shimono, Y., Shimokata, K., Ishiguro, N., and Takahashi, M.Microspherule protein 1, Mi-2β, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription.J. Biol. Chem. 280: 39436-39447 (2005).
    3. Enomoto, A., Murakami, H., Asai, N., Morone, N., Watanabe, T., Kawai, K., Murakumo, Y., Usukura, J., Kaibuchi, K., and Takahashi, M.Akt/PKB regulates actin organization and cell motility via Girdin/APE.Developmental Cell 9: 389-402 (2005).
    4. Morinaga, T., Enomoto, A., Shimono, Y., Hirose, F., Fukuda, N., Dambara, A., Jijiwa, M., Kawai, K., Hashimoto, K., Ichihara, M., Asai, N., Murakumo, Y., Matsuo, S., and Takahashi, M.GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region.Nucleic Acids Res. 33: 4191-4201, 2005.
    5. Matsuura, T., Shimono, Y., Kawai, K., Murakami, H., Urano, T., Niwa, Y., Goto, H., and Takahashi, M.PIAS proteins are involved in the SUMO-1 modification, intracellular translocation and transcriptional repressive activity of RET finger protein.Exp. Cell Res. 308: 65-77, 2005.
    6. Fukuda, T., Asai, N., Enomoto, A., and Takahashi, M.Activation of c-Jun amino-terminal kinase by GDNF induces G2/M cell cycle delay linked with actin reorganization.Genes Cells, 10: 655-663, 2005.
    7. Kodama, Y., Asai, N., Kawai, K., Jijiwa, M., Murakumo, Y., Ichihara, M., and Takahashi, T.The RET proto-oncogene: a molecular therapeutic target in thyroid cancer.Cancer Sci. 96:143-148, 2005.
  • 2004年
    1. Jijiwa, M., Fukuda, T., Kawai, K., Nakamura, A., Kurokawa, K., Murakumo, Y., Ichihara, M. and Takahashi, M.A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia.Mol. Cell. Biol. 24: 8026-8036 (2004).
    2. Maeda, K., Murakami, H., Yoshida, R., Ichihara, M., Abe, A., Hirai, M., Murohara, T. and Takahashi, M.Biochemical and biological responses induced by coupling of Gab1 to phosphatidylinositol 3-kinase in RET-expressing cells.Biochem. Biophys. Res. Commun. 323: 345-354 (2004).
    3. Kodama, Y., Murakumo, Y., Ichihara, M., Kawai, K., Shimono, Y. and Takahashi, M.Induction of CRMP-2 by GDNF and analysis of the CRMP-2 promoter region.Biochem. Biophys. Res. Commun. 320:108-115 (2004).
    4. Hashimoto, T., Ichihara, M., Watanabe, T., Kawai, K., Koshikawa, K., Yuasa, N., Takahashi, T., Yatabe, Y., Murakumo, Y., Zhang, J.-m., Nimura, Y. and Takahashi, M.Expression of CD109 in human cancer.Oncogene 23: 3716-3720 (2004).
    5. Kawamoto, Y., Takeda, K., Okuno, Y., Yamakawa, Y., Ito, Y., Taguchi, R., Kato, M., Suzuki, H., Takahashi, M. and Nakashima, I.Identification of RET autophosphorylation sites by mass spectrometry.J. Biol. Chem. 279: 14213-14224 (2004).
    6. Kato, M., Takdea, K., Kawamoto, Y., Tsuzuki, T., Hossain, K., Tamakoshi, A., Kunisada, T., Kobayashi, Y., Ogino, K., Suzuki, H., Takahashi, M. and Nakahsima, I.c-Kit-targeting immunotherapy for hereditary melanoma in a mouse model.Cancer Res. 64: 801-806 (2004).
    7. Ichihara, M., Murakumo, Y., and Takahashi, M.RET and neuroendocrine tumors.Cancer Lett. 204:197-211 (2004).
  • 2003年
    1. Shimono, Y., Murakami, H., Kawai, K., Wade, P.A., Shimokata, K. and Takahashi, M.Mi-2 associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities.J. Biol. Chem. 278: 51638-51645 (2003).
    2. Kawai, K., Jijiwa, M., Shimono, Y., Kurokawa, K., Murakumo, Y., Ichihara, M. and Takahashi, M.Establishment and characterization of mouse mammary carcinoma cell lines expressing RET with a multiple endocrine neoplasia 2A mutation.Cancer Science 94: 992-997 (2003).
    3. Fukuda, N., Ichihara, M., Morinaga, T., Kawai, K., Hayashi, H., Murakumo, Y., Matsuo, S. and Takahashi, M.Identification of a novel GDNF-inducible gene required for renal branching morphogenesis.J. Biol. Chem. 278: 50386-50392 (2003).
    4. Shimoyama, Y., Morikawa, Y., Ichihara, M., Kodama, Y., Fukuda, N., Hayashi, H., Morinaga, T., Iwashita, T., Murakumoa, Y. and Takahashi, M.Identification of human SEP1 as a glial cell line-derived neurotrophic factor-inducible protein and its expression in the nervous system.Neuroscience 12: 899-906 (2003).
    5. Kurokawa, K., Kawai, K., Hashimoto, M., Ito, Y. and Takahashi M.Cell signaling and gene expression mediated by RET tyrosine kinase.J. Int. Med. 253: 627-633(2003).
    6. Ohshima, N., Takahashi, M. and Hirose, F.Identification of a human homologue of the DREF transcription factor with a potential role in regulation of the histone H1 gene.J. Biol. Chem. 278: 22928-22938(2003).
    7. Kawajiri, A., Yasui, Y., Goto, H., Tatsuka, M., Takahashi, M., Nagata, K. and Inagaki, M.Functional significance of Aurora-B in the separation of type III intermediated filaments during cytokinsis.Mol. Biol. Cell. 14: 1489-1500(2003).
    8. Nishikawa, M., Murakumo, Y., Imai, T., Kawai, K., Nagaya, M., Funahashi, H., Nakao, M. and Takahashi, M.Cys611Ser mutation in RET proto-oncogene is a kindred with medullary thyroid carcinoma and Hirschsprung’s disease.Eur. J. Human Genet. 11: 364-368(2003).
    9. Nakayama, A., Murakami, H., Maeyama, N., Yamashiro, N., Sakakibara, A., Mori, N. and Takahashi, M.Role for RFX transcription factors in non-neuronal cell-specific inactivation of the microtubule-associated protein MAP1A promoter.J. Biol. Chem. 278: 233-240 (2003).
  • 2002年
    1. Iwahashi N1, Murakami H, Nimura Y, Takahashi M. Activation of RET tyrosine kinase regulates interleukin-8 production by multiple signaling pathways. Biochem Biophys Res Commun. 294(3):642-9.(2002).
    2. Murakami, H., Yamamura, Y., Shimono, Y., Kawai, K., Kurokawa, K. and Takahashi, M.Role of Dok1 in cell signaling mediated by RET tyrosine kinase.J. Biol. Chem. 277: 32781-32790 (2002).
    3. Watanabe, T., Ichihara, M., Hashimoto, M., Shimono, K., Shimoyama, Y., Nagasaka, T., Murakumo, Y., Murakami, H., Sugiura, H., Iwata, H., Ishiguro, N. and Takahashi, M.Characterization of gene expression induced by RET with MEN2A or MEN2B mutation.Am. J. Pathol. 161: 249-256 (2002).
    4. Fukuda, T., Kiuchi, K. and Takahashi, M.Essential role for protein kinase A in Rac activity mediated by RET tyrosine kinase.J. Biol. Chem. 277: 19114-19121 (2002).
    5. Kato, M., Takeda, K., Kawamoto, Y., Iwashita, T., Akhand, A.A., Senga, T., Yamamoto, M., Sobue, G., Hamaguchi, M., Takahashi, M. and Nakashima, I.Repair by Src kinase of functional-impaired RET with multiple endocrine neoplasia type 2A mutation with substitutions of tyrosines in the COOH-terminal kinase domain for phenylalanine.Cancer Res. 62: 2414-2422 (2002).
    6. Iwahashi, N., Nagasaka, T., Tezel, G., Iwashita, T., Asai, N., Murakumo, Y., Kiuchi, K., Sakata, K., Nimura, Y. and Takahashi, M.Expression of glial cell line-derived neurotrophic factor correlates with perineural invasion of bile duct carcinoma.Cancer 94: 167-174 (2002).
  • 2001年
    1. Murakumo, Y., Ogura, Y., Ishii, H., Numata, S., Ichiahra, M., Croce, C. M., Fichel, R. and Takahashi, M.Interaction in the error-prone psot-replication repair proteins, hREV1, hREV3, and hREV7.J. Biol. Chem. 276: 35644-35661 (2001).
    2. Kato, M., Takeda, K., Kawamoto, Y., Tsuzuki, T., Dai, Y., Nakayama, S., Toriyama, K., Tamada, Y., Takahashi, M. and Nakashima, I.RET tyrosine kinase enhances hair growth in association with promotion of melanogensis.Oncogene 20: 7536-7541 (2001).
    3. Takahashi, M.The GDNF/RET signaling pathway and human diseases.Cysokine & Growth Factor Reviews 12: 361-373 (2001).
    4. Iwashita, T., Kurokawa, K., Qiao, S., Murakami, H., Asai, N., Kawai, K., Hashimoto, M., Watanabe, T., Ichihara., M. and Takahashi, M.Functional analysis of RET with Hirschsprung's mutations affecting its kinase domain.Gastroenterology 121: 24-33 (2001).
    5. Shigemitsu, K., Sekido, Y., Usami, N., Mori, S., Sato, M., Horio, Y., Hasegawa, Y., Bader, S.A., Gazdar, A.F., Minna, J.D., Hida, T., Yoshioka, H., Imaizumi, M., Ueda, Y., Takahashi, M. and Shimokata, K.Genetic alteration of the b-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion.Oncogene 20: 4249-4257 (2001).
    6. Kurokawa, K., Iwashita, T., Murakami, H., Hayashi, H., Kawai, K. and Takahashi, M.Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction.Oncogene 20: 1929-1938 (2001).
    7. Qiao, S., Iwashita, T., Furukawa, T., Yamamoto, M., Sobue, G. and Takahashi, M.Differential effects of leukocyte common antigen-related protein on biochmical and biological activities of RET-MEN2A and RET-MEN2B mutant proteins.J. Biol Chem. 276: 9460-9467 (2001).
    8. Hayashi, Y., Iwashita, T., Murakami, H., Kato, Y., Kawai, K., Tohnai, I., Ueda, M. and Takahashi, M.Activation of BMK1 via tyrosine 1062 in RET by GDNF and MEN2A mutation.Biochem. Biophys. Res. Commun. 281: 682-689 (2001).
  • 2000年
    1. Shimono, Y., Murakami, H., Hasegawa, Y. and Takahashi, M.RFP is a transcriptional repressor and interacts with enhancer of polycomb that has dual transcriptional functions.J. Biol Chem. 275: 39411-39419. (2000).
    2. Kawai, K., Iwashita, T., Murakami, H., Hiraiwa, N., Yoshiki, A., Kusakabe, M., Ono, K., Iida, K., Nakayama, A. and Takahashi, M.Tissue-specific carcinogenesis in transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutation.Cancer Res. 60: 5254-5260 (2000).
    3. Hayashi, H., Ichihara, M., Iwashita, T., Murakami H., Shimono, Y., Kawai, K., Kurokawa K., Murakumo, Y., Imai, T., Funahashi, H., Nakao, A. and Takahashi, M.Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell-lined derived neurotrophic factor.Oncogene 19: 4469-4475 (2000).
    4. Iwashita, T., Murakami, H., Kurokawa, K., Kawai, K., Miyauchi, A., Futami, H., Qiao, S., Ichihara, M. and Takahashi, M.A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations.Biochem. Biophys. Res. Commun. 268: 804-808 (2000).
    5. Kato, M., Iwashita, T., Takeda, K., Akhand, A. A., Liu, W., Yoshihara, M., Asai N., Suzuki, H., Takahashi, M. and Nakashima, I.Ultraviolet light induces redox reaction-mediated dimerization and superactivation of oncogenic ret tyrosine kinases.Mol. Biol. Cell 11: 93-101 (2000).
  • 1999年
    1. Tezel, G. Nagasaka, T., Iwahashi, N., Asai N., Iwashita, T., Sakata, K. and Takahashi, M.Different nuclear/cytoplasmic distributions of RET finger protein (RFP) in different cell types.Pathol. Int. 49: 881-886 (1999)
    2. Ishiguro, Y., Iwashita, T., Murakami, H., Asai, N., Iida, K., Goto, H., Hayakawa, T. and Takahashi, M.The role of amino acids surrounding tyrosine 1062 in Ret in specific binding of the Shc phosphtyrosine binding domain.Endocrinology 140: 3992-3998 (1999).
    3. Murakami, H., Iwashita, T., Asai, N., Shimono, Y., Iwata, Y., Kawai, K. and Takahashi, M.Enhanced phosphatidylinositol 3-kinase activity and high phosphrylation state of its downstream signaling molecules mediated by Ret with the MEN 2B mutation.Biochem. Biophys. Res. Commun. 262: 68-75 (1999).
    4. Iwata, Y., Nakayama, A., Murakami, H., Iwashita, T., Asai, N. and Takahashi, M.Characterization of the promoter region of the human RFP gene.Biochem. Biophys. Res. Commun. 261: 381-384 (1999).
    5. Iwashita, T., Kato, M., Murakami, H., Asai, N., Ishiguro, Y., Ito, S., Iwata, Y., Kawai, K., Asai, M., Kurokawa, K., Kajita, H. and Takahashi, M.Biological and biochemical properties of Ret with kinase domain mutations identified in multiple endocrine neoplasia type 2B and familial medullary thyroid carcinoma.Oncogene 18: 3919-3922 (1999).
    6. Nakayama, S., Iida, K., Tsuzuki, T., Iwashita, T., Murakami, H., Asai, N., Iwata, Y., Ichihara, M., Ito, S., Kawai, K., Asai, M., Kurokawa, K. and Takahashi M.Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow hematopoietic cells.Brit. J. Hematol. 105: 50-57 (1999).
    7. Takahashi, M., Iwashita, T., Santoro, M., Lyonnet, S., Lenor, G. M. and Billaud, M.Co-segregation of MEN2 and Hirschsprung's disease: the same mutation of RET with both gain and loss-of-function?Hum. Mutat. 13: 331-336 (1999).
    8. Murakami, H., Iwashita, T., Asai, N., Iwata, Y., Narumiya, S. and Takahashi, M.Rho-dependent and -independent tyrosine phosphorylation of focal adhesion kinase, paxillin and p130Cas mediated by Ret kinase.Oncogene 18: 1975-1982 (1999).
    9. Ohyabu, A., Higo, K., Ye, C., Amo, H., Saito, M., Yagyu, S., Morita, H., Maeda, K., Serikawa, T., Takahashi, M. and Matsuyama, M.Genetic mapping of the thymoma susceptible locus, Tsr1, in BUF/Mna rats.J. Natl. Cancer Inst. 91: 279-282 (1999).
  • 1998年
    1. Kato, M., Liu, W., Asai, N., Hayakawa, A., Kozaki, K., Takahashi, M. and Nakashima, I.The herbal medicine Sho-saiko-to inhibits grrowth and metastasis of malignant melanoma primarily developed in ret-transgenic mice.J. Invest. Dermatol. 111: 640-644 (1998).
    2. Kato, M., Takahashi, M., Asai, N., Liu, W., Shimizu, S., Iwamoto, T., Suzuki, H. and Nakashima, I.Transgenic mouse model for skin malignant melanoma.Oncogene 17: 1885-1888 (1998).
    3. Takahashi, M., Asai, N., Iwashita, T., Murakami, H. and Ito, S.Mechanisms of development of multiple endocrine neoplasia type 2 and Hirschsprung’s disease.Recent Results in Cancer Research 154: 229-236 (1998).
    4. Takahashi, M., Asai, N., Iwashita, T., Murakami, H. and Ito, S.Molecular mechanisms of development of multiple endocirine neoplasia 2 by RET mutations.J. Int. Med. 243: 509-513 (1998).
    5. Nozaki, C., Asai, N., Murakami, H., Iwashita, T., Iwata, Y., Horibe, K., Klein, R.D., Rosenthal, A. and Takahashi, M.Calcium-dependent Ret activation by GDNF and neurturin.Oncogene 16, 293-299 (1998).
  • 1997年
    1. Ito, S., Iwashita, T., Asai, N., Murakami, H., Iwata, Y., Sobue, G. and Takahashi, M.Biological properties of Ret with cysteine mutations correlate with multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and Hirschsprung's disease phenotype.Cancer Res. 57, 2870-2872 (1997).
    2. Klein, R.D., Sherman, D., Ho, W.-H., Stone, D., Bennett, G.L., Moffat, B., Vandlen, R., Simmons, L., Gu, Q., Hongo, A.-J., Devaux, B., Poulsen, K., Armanini, M., Nozaki, C., Asai, N., Goddard, A., Phillips, H., Henderson, C.E., Takahashi, M. and Rosenthal, A.A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor.Nature 387, 717-721 (1997).
    3. Ohiwa, M., Murakami, H., Iwashita, T., Asai, N., Iwata, Y., Imai, T., Funahashi, H., Takagi, H. and Takahashi, M.Characterization of Ret-Shc-Grb2 complex induced by GDNF, MEN 2A and MEN 2B mutations.Biochem. Biophys. Res. Commun. 237, 747-751 (1997).
  • 1996年
    1. Iwashita, T., Murakami, H., Asai, N. and Takahashi, M.Mechanism of Ret dysfunction by Hirschsprung mutations affecting its extracellular domain.Hum. Mol. Genet. 5, 1577-1580 (1996).
    2. Asai, N., Murakami, H., Iwashita, T. and Takahashi, M.A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with Shc adaptor proteins.J. Biol. Chem. 271, 17644-17649 (1996).
    3. Treanor, J.J.S., Goodman, L., de Sauvage, F., Stone, D.M., Poulsen, K.T., Beck, C.D., Gray, C., Armanini, M.P., Pollock, R.A., Hefti, F., Phillips, H.S., Goddard, A., Moore, M.W., Buj-Bello, A., Davies, A.M. Asai, N., Takahashi, M., Vandlen, R., Henderson, C.E. and Rosenthal, A.Characterization of a multicomponent receptor for GDNF.Nature 382, 80-83 (1996).
    4. Iwashita, T., Asai, N., Murakami, H., Matsuyama, M. and Takahashi, M.Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN2A or MEN2B mutation.Oncogene 12, 481-487 (1996).
  • 1995年
    1. Asai, N., Iwashita, T., Matsuyama, M. and Takahashi, M.Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations.Mol. Cell. Biol. 15, 1613-1619 (1995).
    2. Takahashi, M.Oncogenic activation of the ret protooncogene in thyroid cancer.Crit. Rev. Oncog. 6, 35-46 (1995).
    3. Tsuzuki, T., Takahashi, M., Asai, N., Iwashita, T., Matsuyama, M. and Asai, J.Spatial and temporal expression of the ret proto-oncogene product in embryonic, infant and adult rat tissues.Oncogene 10, 191-198 (1995).
  • 1993年
    1. Iwamoto, T., Taniguchi, M., Asai, N., Ohkusu, K., Nakashima, I. and Takahashi, M.cDNA cloning of mouse ret proto-oncogene and its sequence similarity to the cadherin superfamily.Oncogene 8, 1087-1091 (1993).
    2. Takahashi, M., Asai, N., Iwashita, T., Isomura, T., Miyazaki, K. and Matsuyama, M.Characterization of the ret proto-oncogene products expressed in mouse L cells.Oncogene 8, 2925-2929 (1993).
  • 1991年
    1. Iwamoto, T., Takahashi, M., Ito, M., Hamatani, M., Ohbayashi, M., Wajjwalku, W., Isobe, K. and Nakashima I.Aberrant melanogenesis and melanocytic tumor development in transgenic mice that carry a metallothionein/ret fusion gene.EMBO J. 10, 3167-3175 (1991).
    2. Takahashi, M., Buma, Y. and Taniguchi, M.Identification of the ret proto-oncogene products in neuroblastoma and leukemia cells.Oncogene 6, 297-301 (1991).
  • 1988年
    1. Takahashi, M., Buma, Y., Iwamoto, T., Inaguma, Y., Ikeda, H. and Hiai, H.Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domain.Oncogene 3, 571-578 (1988).
    2. Takahashi, M., Inaguma, Y., Hiai, H. and Hirose, F.Developmentally regulated expression of a human finger-containing gene encoded by the 5’ half of the ret proto-oncogene.Mol. Cell. Biol. 7, 1853-1856 (1988).
  • 1987年
    1. Takahashi, M. and Cooper, G. M.ret transforming gene encodes a fusion protein homologous to tyrosine kinases.Mol. Cell. Biol. 7, 1378-1385 (1987).
  • 1985年
    1. Takahashi, M., Ritz, J. and Cooper, G.M.Activation of a novel human transforming gene, ret, by DNA rearrangement.Cell 42, 581-588 (1985).