Systematic analysis of Ras/ERK pathway with FRET imaging

2014 Fiscal Year Final Research Report

• Project/Area Number: 23701052
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kyoto University
• Principal Investigator: AOKI Kazuhiro 京都大学, 医学(系)研究科(研究院), 准教授 (80511427)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: FRETイメージング / 分子標的薬 / Ras / ERK / PI3K / mTOR / シミュレーション

Outline of Final Research Achievements

Raf/ERK signaling pathway is involved in cell proliferation, differentiation,and tumorigenesis. In this study, we attempted to visualize activities of signaling molecules in the Ras/ERK pathway by live-cell imaging with or without chemical inhibitors, and build mathematical models based on the imaging data. We identified several feedback and feedforward reactions in the Ras/ERK pathway, and found that these feedback/feedforward reactions attenuated the effect of a molecular targeting drugs by reactivating other pathways. Based on mathematical model, we propose combination treatment of molecular targeting drugs to achieve better antitumor effect in cancer cells harboring gene mutation in the Ras/ERK pathway.

Free Research Field

腫瘍生物学