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Identification of metastasis-related genes using a spontaneous colorectal cancer metastasis model.

Research Project

Project/Area Number 20K07440
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

Fujishita Teruaki  愛知県がんセンター(研究所), がん病態生理学分野, 主任研究員 (50511870)

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)
Keywords大腸がん / 浸潤・転移 / マウスモデル / 転移 / トランスポゾン
Outline of Research at the Start

大腸がんによる死亡の多くは転移によることから予防・治療法の開発が待たれている。大腸がん自然転移マウスモデルにトランスポゾンを用いた生体レベルでの機能スクリーニングを実施し、大腸がん転移に関わる遺伝子を探索している。
本研究では、スクリーニングで同定した候補因子の大腸がん肝転移への関与やそのメカニズムを明らかにし、さらに臨床検体を用いて検証することにより、転移性大腸がんの新たな治療標的の同定を目指す。

Outline of Final Research Achievements

Since the majority of deaths from colorectal cancer are caused by metastasis to other organs, the development of novel prevention and treatment is required. In this study, we succeeded in developing a genetically engineered mouse model in which colorectal cancer develops and metastasizes spontaneously to the liver at a low frequency of approximately 20%, and a mouse model in which the frequency of liver metastasis increases approximately twofold by introducing PiggyBac transposon into this mouse model. By analyzing these mouse models, metastasis related genes and signaling pathways were identified.

Academic Significance and Societal Importance of the Research Achievements

本研究は大腸がんの発症から浸潤・転移といった大腸がんの悪性化に必要な遺伝子を、大腸がんを自然発症し遠隔臓器へ転移するモデルを開発することで、生体レベルで明らかにした。さらに遺伝子変異外にも転移で活性化するシグナル経路について同定できたことから、本研究成果はこれまで困難とれてきた転移能を獲得した大腸がんに対して新たな治療方法の開発に寄与するものである。

Report

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

    (12 results)

All 2022 2021 2020 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] The cAMP/PKA/CREB and TGFβ/SMAD4 Pathways Regulate Stemness and Metastatic Potential in Colorectal Cancer Cells2022

    • Author(s)
      Fujishita Teruaki、Kojima Yasushi、Kajino-Sakamoto Rie、Mishiro-Sato Emi、Shimizu Yasuhiro、Hosoda Waki、Yamaguchi Rui、Taketo Makoto Mark、Aoki Masahiro
    • Journal Title

      Cancer Research

      Volume: 82 Issue: 22 Pages: 4179-4190

    • DOI

      10.1158/0008-5472.can-22-1369

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conditional Ror1 knockout reveals crucial involvement in lung adenocarcinoma development and identifies novel HIF-1α regulator2021

    • Author(s)
      Hisanori Isomura, Ayumu Taguchi, Taisuke Kajino, Naoya Asai, Masahiro Nakatochi, Seiichi Kato, Keiko Suzuki, Kiyoshi Yanagisawa, Motoshi Suzuki, Teruaki Fujishita, Tomoya Yamaguchi, Masahide Takahashi, Takashi Takahashi
    • Journal Title

      Cancer Sci.

      Volume: 112 Issue: 4 Pages: 1614-1623

    • DOI

      10.1111/cas.14825

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells2021

    • Author(s)
      Rie Kajino-Sakamoto, Teruaki Fujishita, Makoto Mark Taketo, Masahiro Aoki
    • Journal Title

      Oncogene

      Volume: 40 Issue: 2 Pages: 408-420

    • DOI

      10.1038/s41388-020-01541-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Experimental Animal Model of Re-irradiation to Evaluate Radiation-induced Damage in the Normal Intestine2020

    • Author(s)
      Hiroshi Doi , Mikoto Tamura , Kiyoshi Nakamatsu , Hajime Monzen , Yasumasa Nishimura
    • Journal Title

      Anticancer Res

      Volume: 40(4) Issue: 12 Pages: 1981-1988

    • DOI

      10.1038/s41417-020-00282-5

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Transposon-based screening of metastasis-related genes in a colorectal cancer mouse model2022

    • Author(s)
      藤下 晃章 、梶野 リエ、三城 恵美、武藤 誠 、青木 正博
    • Organizer
      第81回 日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Tumor microenvironment-related pathways critical for stemness and metastatic potential of colorectal cancer2022

    • Author(s)
      青木 正博、武藤 誠、藤下 晃章
    • Organizer
      第81回 日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Mechanism of synthetic lethality induced by MyD88 loss in intestinal tumor cells with Wnt pathway mutations2022

    • Author(s)
      梶野 リエ、藤下 晃章 、武藤 誠 、青木 正博
    • Organizer
      第81回 日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Identification of Metastasis-related Molecules Using a Mouse Model of Metastatic Colorectal Cancer2022

    • Author(s)
      藤下 晃章
    • Organizer
      第31回 日本がん転移学会学術集会・総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 青木 正博、武藤 誠、藤下 晃章2022

    • Author(s)
      マウスモデルを用いた大腸がんの幹細胞性・転移形成能に関与するシグナル経路の解析
    • Organizer
      第26回 日本がん分子標的治療学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ALCAM (CD166)は大腸がん幹細胞の幹細胞性と転移能に寄与する2021

    • Author(s)
      青木正博、武藤誠、藤下晃章
    • Organizer
      がん分子標的治療学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Identification of drivers of cancer stemness using a mouse model of spontaneously metastasizing colorectal cancer2020

    • Author(s)
      青木正博、武藤誠、藤下晃章
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Remarks] 大腸がんの転移能と幹細胞性を制御するメカニズムを発見

    • URL

      https://cancer-c.pref.aichi.jp/uploaded/attachment/3643.pdf

    • Related Report
      2022 Annual Research Report

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

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