Elucidating the mechanisms of colorectal cancer metastasis using mouse models

2017 Fiscal Year Final Research Report

• Project/Area Number: 26290045
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Aoki Masahiro 愛知県がんセンター(研究所), 分子病態学部, 部長 (60362464)
• Co-Investigator(Kenkyū-buntansha): 梶野 リエ 愛知県がんセンター(研究所), 分子病態学部｀, 研究員 (20633184) ; 小島 康 愛知県がんセンター(研究所), 分子病態学部, 主任研究員 (30464217) ; 藤下 晃章 愛知県がんセンター(研究所), 分子病態学部, 主任研究員 (50511870) ; 佐久間 圭一朗 愛知県がんセンター(研究所), 分子病態学部, 室長 (90402891)
• Co-Investigator(Renkei-kenkyūsha): TAKEDA Junji 大阪大学, 医学研究科, 教授 (50163407)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 大腸がん / 転移 / マウスモデル / スプライシング / RNA結合タンパク / トランスポゾン / 遺伝子改変マウス

Outline of Final Research Achievements

We identified HNRNPLL, an RNA binding protein, as a novel suppressor of colorectal cancer metastasis through a functional screen in mice. Reduced expression of HNRNPLL in colorectal cancer cells conferred increased their invasion ability in vitro and metastatic ability in vivo. HNRNPLL was shown to suppress invasion of colorectal cancer cells at least partly via controlling the alternative splicing of CD44 pre-mRNA. HNRNPLL expression was downregulated during epithelial-mesenchymal transition (EMT) of colorectal cancer cells, and immunohistochemical analysis of colorectal cancer clinical samples further suggested the link between the HNRNPLL level and EMT. HNRNPLL was also shown to stabilize mRNAs encoding the DNA replication factors, and to enhance proliferation of colorectal cancer cells.

Free Research Field

腫瘍学