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Development of the treatment for colorectal cancer liver metastasis targeting Wnt-dependent cancer stem cells

Research Project

Project/Area Number 16K07174
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor therapeutics
Research InstitutionOsaka University

Principal Investigator

Wu Xin  大阪大学, 医学系研究科, 招へい教員 (00764739)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsマイクロRNA / 大腸癌 / LRP6 / KRAS / 肝転移 / wnt / microRNA / 癌幹細胞
Outline of Final Research Achievements

This research aimed to develop the new treatment of colorectal cancer with miR-487b. Mir-487b was a prognostic factors for colorectal cancer. This miRNA targeted LPR6, a coreceptor for Wnt ligand, and KRAS. Although transfection of miR-487b to the colorectal cancer cell lines inhibited cell growth, invasion, and colony formation, the anti-tumor effect of miR-487b appeared to be not sufficient to inhibit in vivo tumor growth. Moreover, LRP6 expression was not related to prognosis in colorectal cancer. In vitro signal transduction assays, siRNA-LRP6 inhibited Wnt signal activity when Wnt3a was added in esophageal cancer cells, but not in colon cancer cells, suggesting that LRP6 may not paly a crucial role in colon cancer, possibly because of the endogenous alterations of β-catenin and APC genes.

Academic Significance and Societal Importance of the Research Achievements

miR-487bの新たな機能として大腸癌の増殖や浸潤、コロニー形成、WntリガンドやKRASが関与するシグナル系に関わっていることが明らかに出来たという意味で、学術的な意義は大きい。大腸癌に比べて、食道癌ではLRP6の発現が癌の悪性化に寄与していることが明らかとなった。癌の悪性化の進展は癌種や個体差など様々な原因により影響をうける。そのため、個別化医療等により患者に最適な治療を設定する必要がある。今回の結果は、この様なオーダーメイド医療において、非常に有用となるデータを提供できると考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2018

All Presentation (2 results)

  • [Presentation] miR487bが大腸癌の転移を抑制する2018

    • Author(s)
      呉しん、波多豪、横山雄起、大石和樹、三吉範克、原口直紹、高橋秀和、畑泰司、松田宙、水島恒和、土岐祐一郎、森正樹、山本浩文
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大腸癌におけるLRP6蛋白の免疫組織化学的検討2018

    • Author(s)
      大石和樹、横山雄起、呉しん、水島恒和、土岐祐一郎、森正樹、山本浩文
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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