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Mechanisms and significance of collective cancer cell migration mediated by cadherin-specific endocytosis

Research Project

Project/Area Number 15H04719
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNagoya University

Principal Investigator

Enomoto Atsushi  名古屋大学, 医学系研究科, 准教授 (20432255)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords集団的移動 / 集団的浸潤 / 癌 / Girdin / アクチン細胞骨格 / 神経芽細胞 / 細胞間接着 / エンドサイトーシス / 癌の浸潤
Outline of Final Research Achievements

Pathological observations show that cancer cells invade the surrounding stroma in collective groups rather than through single cell migration. We studied the role of the actin-binding protein Girdin in collective cancer cell migration. We found that Girdin was essential for the collective migration of the skin cancer cell line A431 on collagen gels as well as their invasion in an organotypic culture model. We provide evidence that Girdin binds to β-catenin that plays important roles in E-cadherin-mediated cell-cell adhesion. Girdin-depleted cells displayed scattering and impaired cell-cell adhesion. Girdin depletion led to impaired cytoskeletal association of the β-catenin complex, which was accompanied by changes in the supracellular actin cytoskeletal organization. Finally, we showed the significance of Girdin expression in the progression of human skin cancer. Collectively, our results suggest that Girdin is an important modulator of the collective behavior of cancer cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (18 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Int'l Joint Research] Central South University(China)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex2018

    • Author(s)
      Liang Weng , Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi.
    • Journal Title

      PLoS Biology

      Volume: 16 Issue: 3 Pages: e2005090-e2005090

    • DOI

      10.1371/journal.pbio.2005090

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer.2018

    • Author(s)
      Nobutoshi Esaki, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Tsuda, Yuhsuke Ohmi, Robiul H. Bhuiyan, Norihiro Kotani, Koichi Honke, Atsushi Enomoto, Masahide Takahashi, Keiko Furukawa, Koichi Furukawa.
    • Journal Title

      Cancer sci.

      Volume: 109 Issue: 1 Pages: 141-153

    • DOI

      10.1111/cas.13448

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of perivascular tumour cells defined by CD109 expression in progression of glioma2017

    • Author(s)
      Shiraki Yukihiro、Mii Shinji、Enomoto Atsushi、Momota Hiroyuki、Han Yi-Peng、Kato Takuya、Ushida Kaori、Kato Akira、Asai Naoya、Murakumo Yoshiki、Aoki Kosuke、Suzuki Hiromichi、Ohka Fumiharu、Wakabayashi Toshihiko、Todo Tomoki、Ogawa Seishi、Natsume Atsushi、Takahashi Masahide
    • Journal Title

      The Journal of Pathology

      Volume: 243 Issue: 4 Pages: 468-480

    • DOI

      10.1002/path.4981

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus2017

    • Author(s)
      Maki Takagishi, Masato Sawada, Shinya Ohata, Naoya Asai, Atsushi Enomoto, Kunihiko Takahashi, Liang Weng, Kaori Ushida, Hosne Ara, Shigeyuki Matsui, Kozo Kaibuchi,3Kazunobu Sawamoto, and Masahide Takahashi.
    • Journal Title

      Cell Reports

      Volume: 20 Issue: 4 Pages: 960-972

    • DOI

      10.1016/j.celrep.2017.06.089

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of low mTORC1 activity in defining the characteristics of brain tumor stem cells.2017

    • Author(s)
      Han YP, Enomoto A, Shiraki Y, Wang SQ, Wang X, Toyokuni S, Asai N, Ushida K, Ara H, Ohka F, Wakabayashi T, Ma J, Natsume A, Takahashi M.
    • Journal Title

      Neuro Oncol

      Volume: 19 Pages: 636-647

    • DOI

      10.1093/neuonc/now237

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] High-fat diet feeding promotes stemness and precancerous changes in murine gastric mucosa mediated by leptin receptor signaling pathway2016

    • Author(s)
      Arita S, Kinoshita Y, Ushida K, Enomoto A, Inagaki-Ohara K
    • Journal Title

      Arch Biochem Biophys

      Volume: 610 Pages: 16-24

    • DOI

      10.1016/j.abb.2016.09.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Suppression of skin tumorigenesis in CD109-deficient mice.2016

    • Author(s)
      Sunagawa M, Mii S, Enomoto A, Kato T, Murakumo Y, Shiraki Y, Asai N, Asai M, Nagino M, Takahashi M.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 50 Pages: 82836-82850

    • DOI

      10.18632/oncotarget.12653

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Collective invasion of cancer: Perspectives from pathology and development2016

    • Author(s)
      Wang X, Enomoto A, Asai N, Kato T, Takahashi M
    • Journal Title

      Pathol Int

      Volume: 66 Issue: 4 Pages: 183-192

    • DOI

      10.1111/pin.12391

    • NAID

      120005893271

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells2016

    • Author(s)
      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, Takahashi M
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 22288-22288

    • DOI

      10.1038/srep22288

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Girdin regulates the collective migration of cancer cells by interacting with beta-catenin/alpha-catenin2017

    • Author(s)
      Xiaoze Wang、Atsushi Enomoto、Liang Weng、Naoya Asai、Masahide Takahashi
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脳腫瘍マウスモデルにおけるテモゾロミド感受性に対するCD109の機能解析2017

    • Author(s)
      白木 之浩、三井 伸二、浅井 直也、榎本 篤、百田 洋之、夏目 敦至、若林 俊彦、高橋 雅英
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 病理組織の理解にもとづくがん多様性と進展機序の研究展開2017

    • Author(s)
      榎本篤
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Mechanisms for the control of amino acid signaling and drug resistance in cancer stem cells2017

    • Author(s)
      榎本篤、髙橋雅英
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 間葉系幹細胞およびペリサイトの新規マーカー候補分子Meflinの同定2016

    • Author(s)
      前田啓子、榎本篤、後藤秀実、高橋雅英
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪府・大阪市・大阪国際会議場
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脳腫瘍幹細胞におけるmTORC1活性制御とその分子機構の解析2016

    • Author(s)
      榎本篤、翁良、韓一梵、浅井直也、三井伸二、高橋雅英
    • Organizer
      日本病理学会秋期特別総会
    • Place of Presentation
      石川県・金沢市・金沢文化ホール
    • Related Report
      2016 Annual Research Report
  • [Presentation] Meflin is a specific marker for mesenchymal stem cells (MSCs) whose expression is regulated by substrate stiffness2016

    • Author(s)
      Atsushi Enomoto, Naoya Asai, Takeshi Kobayashi, Nobuhisa Nakamura and Masahide Takahashi
    • Organizer
      ASCB Annual Meeting 2016
    • Place of Presentation
      米国・サンフランシスコ・モスコーニセンター
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ビメンチンリン酸化不全マウスの皮膚線維芽細胞は染色体異数性を呈し、皮膚の早期老化を示す2015

    • Author(s)
      田中宏樹、後藤英仁、猪子誠人、牧原弘幸、榎本篤、伊澤一郎、稲垣昌樹
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      愛知県・名古屋市・名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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