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Functional analysis of Hippo pathway in thymus

Research Project

Project/Area Number 20K07572
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKobe University

Principal Investigator

Nishio Miki  神戸大学, 医学研究科, 講師 (10467897)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsHippo経路 / Hippo / 胸腺 / 腫瘍 / Hippo pathway / 遺伝子改変マウス
Outline of Research at the Start

胸腺上皮細胞やNKT細胞におけるHippo経路の役割を解析し、この経路の生理的役割や破綻病態を、特に腫瘍発症の有無や腫瘍免疫監視の観点を重視して解析し、MSTが変異したヒトにみられる病態や危険性を明示するとともに、これらの研究成果を基にした、Hippo経路を標的とする抗腫瘍薬や免疫調節薬等の創薬研究への礎をつくる。

Outline of Final Research Achievements

The thymus is composed of T cells and surrounding stromal cells. Although thymic T cell research has made considerable progress, the regulation of thymic epithelial cell proliferation, differentiation, and function remains largely unknown. The Hippo pathway has recently attracted attention as an important tumor regulatory pathway. We analyzed the function of the Hippo pathway in thymic epithelial cells and NKT cells using genetically engineered mice and found that LATS, one of the Hippo pathway molecules, is involved in the pathogenesis of thymic carcinoma. We also found that MST, a Hippo pathway molecule, is important for the differentiation and maturation of NKT cells.

Academic Significance and Societal Importance of the Research Achievements

胸腺上皮細胞やNKT細胞におけるHippo経路の生理的役割や破綻病態を、特に腫瘍発症の有無や腫瘍免疫監視の観点を重視して解析するは、MSTが変異したヒトにみられる病態や危険性を明示するとともに、これらの研究成果を基にした、Hippo経路を標的とする抗腫瘍薬や免疫調節薬等の創薬研究開発への貢献も期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (15 results)

All 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (10 results)

  • [Journal Article] Alantolactone is a natural product that potently inhibits YAP1/TAZ through promotion of reactive oxygen species accumulation.2021

    • Author(s)
      Nakatani K, Maehama T, Nishio M, Otani J, Yamaguchi K, Fukumoto M, Hikasa H, Hagiwara S, Nishina H, Mak TW, Honma T, Kondoh Y, Osada H, Yoshida M, Suzuki A
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 10 Pages: 4303-4316

    • DOI

      10.1111/cas.15079

    • NAID

      120007159906

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TAZ inhibits acinar cell differentiation but promotes immature ductal cell proliferation in adult mouse salivary glands.2021

    • Author(s)
      Miyachi Y, Nishio M, Otani J, Matsumoto S, Kikuchi A, Mak TW, Maehama T, Suzuki A.
    • Journal Title

      Genes Cells.

      Volume: 26(9) Issue: 9 Pages: 714-726

    • DOI

      10.1111/gtc.12879

    • NAID

      120007148944

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The role of Hippo-YAP signaling in squamous cell carcinomas.2020

    • Author(s)
      Tomohiko Maehama , Miki Nishio , Junji Otani , Tak Wah Mak , Akira Suzuki
    • Journal Title

      Cancer science

      Volume: 112 Issue: 1 Pages: 51-60

    • DOI

      10.1111/cas.14725

    • NAID

      120006950333

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice.2020

    • Author(s)
      Miki Nishio , Yoko To , Tomohiko Maehama , Yukari Aono , Junji Otani , Hiroki Hikasa , Akihiro Kitagawa , Koshi Mimori , Takehiko Sasaki , Hiroshi Nishina , Shinya Toyokuni , John P Lydon , Kazuwa Nakao , Tak Wah Mak , Tohru Kiyono , Hidetaka Katabuchi , Hironori Tashiro , Akira Suzuki
    • Journal Title

      Cancer science

      Volume: 111 Issue: 10 Pages: 3576-3578

    • DOI

      10.1111/cas.14581

    • NAID

      120006892076

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 細胞競合とがん 哺乳類Hippo経路による細胞接着の制御と細胞競合2020

    • Author(s)
      前濱 朝彦 , 西尾 美希 , 鈴木 聡
    • Journal Title

      医学のあゆみ

      Volume: 274 Pages: 457-462

    • Related Report
      2020 Research-status Report
  • [Presentation] 動物モデルによる先端がん研究 Hippoシグナルによるがんの発症進展制御2021

    • Author(s)
      西尾 美希, 前濱 朝彦, 大谷 淳二, 曽山 弘敏, 鈴木 聡
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Basal like乳癌におけるHippo経路の役割2021

    • Author(s)
      曽山 弘敏, 西尾 美希, 増田 隆明, 三森 功士, 原 重雄, 前濱 朝彦, 福本 巧, 鈴木 聡
    • Organizer
      第80回日本癌学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Hippo経路を標的として膀胱がん細胞の増殖を抑制する新規化合物の同定2021

    • Author(s)
      白石 祐介, 前濱 朝彦, 西尾 美希, 藤澤 正人, 鈴木 聡
    • Organizer
      第80回日本癌学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] A natural product Alantolactone is a potent YAP1/TAZ inhibitor via ROS production2020

    • Author(s)
      Junji Otani, Keisuke Nakatani, Tomohiko Maehama, Miki Nishio, Akira Suzuki
    • Organizer
      The 14th International Conference on Protein Phosphatase
    • Related Report
      2020 Research-status Report
  • [Presentation] Squamous cell carcinoma onset and progression driven by multistep YAP activation2020

    • Author(s)
      Tomohiko Maehama, Miki Nishio, Hirofumi Omori, Akira Suzuki
    • Organizer
      The 14th International Conference on Protein Phosphatase
    • Related Report
      2020 Research-status Report
  • [Presentation] がん抑制遺伝子の機能解析2020

    • Author(s)
      鈴木 聡、西尾美希、藤 庸子、大森博文、田代浩徳、前濱朝彦
    • Organizer
      第19回日本産婦人科がん分子標的研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] YAP1/TAZ阻害による抗腫瘍作用を示す天然物の同定2020

    • Author(s)
      西尾美希、中谷圭佑、大谷淳二、日笠弘基、前濱朝彦、鈴木聡
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] YAPの多段階活性化による扁平上皮癌の発症・進展の制御2020

    • Author(s)
      前濱朝彦、西尾美希、大森裕文、鈴木聡
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] YAPの多段階活性化による扁平上皮癌の発症・進展の制御2020

    • Author(s)
      前濱朝彦、西尾美希、大森裕文、鈴木聡
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Hippo経路による扁平上皮癌の制御2020

    • Author(s)
      前濱朝彦、西尾美希、大森裕文、田代浩徳、中尾一和、鈴木聡
    • Organizer
      第57回日本臨床分子医学会学術集会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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