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Elucidation of the role of MyD88 in Apc mutant intestinal tumor epithelial cells

Research Project

Project/Area Number 18K07254
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 InstitutionAichi Cancer Center Research Institute

Principal Investigator

Kajino Rie  愛知県がんセンター(研究所), がん病態生理学分野, 研究員 (20633184)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsApc変異 / 大腸がん / 合成致死 / マウスモデル
Outline of Final Research Achievements

Mutations in the APC tumor suppressor gene are associated with the onset of adenoma carcinoma sequence in colorectal cancer. Conditional knockout of MyD88 in intestinal epithelial cells reduced the number of intestinal tumors in Apc mutant mice, genetically engineered mouse models of early colorectal cancer. Loss of MyD88 functions in Apc tumor cells resulted in the reduction of proliferation and caused apoptotic cell death. We found that epithelial MyD88 plays essential roles in the survival of the intestinal tumors, and that HIF-1a, NF-kB and Wnt pathways function downstream of MyD88. Further elucidation of the mechanism is expected to lead to the development of new treatments for colorectal cancer.

Academic Significance and Societal Importance of the Research Achievements

大腸がんはがんの中でも患者数が多く、本邦の部位別がん死亡率をみると大腸がんは男性で第3位、女性では第1位であり、効果的な治療法が必要とされている。本研究の成果は、APC変異を持つ大腸がん細胞ではMyD88がアキレス腱となりうることを示しており、MyD88やその下流の因子の働きを阻害する化合物が開発されて臨床で使用できるようになれば、APC変異を持つ多くの大腸がんに対する新しい治療戦略につながることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2021 2019 2018 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) Remarks (1 results)

  • [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 Annual Research Report
    • Peer Reviewed
  • [Presentation] Synthetic lethality between Apc mutation and MyD88 loss in intestinal tumor epithelial cells2019

    • Author(s)
      梶野リエ、藤下晃章、武藤誠、青木正博
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Apc変異マウスの腸管腫瘍形成において腸上皮細胞のMyD88が果たす役割の解明2018

    • Author(s)
      梶野リエ、藤下晃章、武藤誠、青木正博
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 特定の遺伝子変異を持つ大腸がん細胞が生き残るのに重要な因子を発見

    • URL

      https://www.pref.aichi.jp/cancer-center/cc/press/pdf/201112press_aoki.pdf

    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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