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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07174
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Osaka 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
• Keywords: マイクロRNA / 大腸癌 / LRP6 / KRAS

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.

Free Research Field

癌の核酸治療

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。