Identification and analysis of novel metastasis regulators by the metastasis-step focused in vivo screening

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: TAKEMOTO Ai 公益財団法人がん研究会, がん化学療法センター 基礎研究部, 主任研究助手 (20706494)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: がん転移

Outline of Final Research Achievements

Cancer metastasis is regulated by multi- and various steps. To understand the mechanism contributing to metastasis establishment and to propose the effective suppression strategy, analyses using the model possible to discriminate metastasis steps could be useful. Therefore, in this study, cancer cell lines lacking the specific metastasis step were used for in vivo screen, in which genome-wide shRNA library was transformed to each cell line and promoted metastatic frequency by the shRNA knock-down was monitored in vivo metastasis model. And then, identification of candidates of metastasis regulators and analysis using the specific model were performed in aiming to understand the novel metastasis-regulatory mechanism. Out of identified candidates, one was suggested to contribute in mobility and invasion ability important during the early metastasis step and the other in the regulation of expression of a platelet aggregation-promoting factor.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

がん患者の死因の9割を超える転移に対して未だ効果的な抑制法が不足している現状において、転移制御因子の同定と各因子の機能に踏み込んだ詳細な解析による新規制御経路の理解と転移抑制標的としての妥当性の評価は、抑制法の提案に欠かせない。本研究では、機能解析を加速化できるように各転移過程にフォーカスしたin vivoスクリーニングを構築し、実際に複数の新規転移候補因子の同定と制御機構を示唆するに至った点で学術的意義がある。さらに、このような系によるスクリーニングの遂行と同定した因子のin vivoでの解析を進めることで効果的な転移抑制法開発の足掛かりとなる可能性がある。